TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Savić, Jelena
AU  - Tomašić, Tihomir
AU  - Durcik, Martina
AU  - Zidar, Nace
AU  - Peterlin-Mašič, Lucija
AU  - Ilaš, Janez
AU  - Kikelj, Danijel
AU  - Čudina, Olivera
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5431
AB  - Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication
and represent important antibacterial drug targets. To be successful as drug candidates, newly synthesized compounds must possess optimal lipophilicity, which enables efficient delivery to the site of action. In this study, retention behavior of twenty-three previously synthesized dual DNA gyrase and topoisomerase IV inhibitors was tested in RP-HPLC system, consisting of C8 column and acetonitrile/phosphate buffer (pH 5.5 and pH 7.4) mobile phase. logD was calculated at both pH values and the best correlation with logD was obtained for retention parameter φ0, indicating that this RP-HPLC system could be used as an alternative to the shake-flask determination of lipophilicity. Subsequent QSRR analysis revealed that intrinsic lipophilicity (logP) and molecular weight (bcutm13) have a positive, while solubility (bcutp3) has a negative influence on this  retention parameter.
PB  - Akadémiai Kiadó
T2  - Acta Chromatographica
T1  - High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors
VL  - 36
IS  - 1
SP  - 45
EP  - 51
DO  - 10.1556/1326.2022.01096
ER  - 

@article{
author = "Dobričić, Vladimir and Savić, Jelena and Tomašić, Tihomir and Durcik, Martina and Zidar, Nace and Peterlin-Mašič, Lucija and Ilaš, Janez and Kikelj, Danijel and Čudina, Olivera",
year = "2024",
abstract = "Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication
and represent important antibacterial drug targets. To be successful as drug candidates, newly synthesized compounds must possess optimal lipophilicity, which enables efficient delivery to the site of action. In this study, retention behavior of twenty-three previously synthesized dual DNA gyrase and topoisomerase IV inhibitors was tested in RP-HPLC system, consisting of C8 column and acetonitrile/phosphate buffer (pH 5.5 and pH 7.4) mobile phase. logD was calculated at both pH values and the best correlation with logD was obtained for retention parameter φ0, indicating that this RP-HPLC system could be used as an alternative to the shake-flask determination of lipophilicity. Subsequent QSRR analysis revealed that intrinsic lipophilicity (logP) and molecular weight (bcutm13) have a positive, while solubility (bcutp3) has a negative influence on this  retention parameter.",
publisher = "Akadémiai Kiadó",
journal = "Acta Chromatographica",
title = "High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors",
volume = "36",
number = "1",
pages = "45-51",
doi = "10.1556/1326.2022.01096"
}

Dobričić, V., Savić, J., Tomašić, T., Durcik, M., Zidar, N., Peterlin-Mašič, L., Ilaš, J., Kikelj, D.,& Čudina, O.. (2024). High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors. in Acta Chromatographica
Akadémiai Kiadó., 36(1), 45-51.
https://doi.org/10.1556/1326.2022.01096

Dobričić V, Savić J, Tomašić T, Durcik M, Zidar N, Peterlin-Mašič L, Ilaš J, Kikelj D, Čudina O. High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors. in Acta Chromatographica. 2024;36(1):45-51.
doi:10.1556/1326.2022.01096 .

Dobričić, Vladimir, Savić, Jelena, Tomašić, Tihomir, Durcik, Martina, Zidar, Nace, Peterlin-Mašič, Lucija, Ilaš, Janez, Kikelj, Danijel, Čudina, Olivera, "High-performance liquid chromatography evaluation of lipophilicity and QSRR modeling of a series of dual DNA gyrase and topoisomerase IV inhibitors" in Acta Chromatographica, 36, no. 1 (2024):45-51,
https://doi.org/10.1556/1326.2022.01096 . .

TY  - CONF
AU  - Bošković, Jelena
AU  - Dobričić, Vladimir
AU  - Nedeljković, Nikola
AU  - Nikolić, Miloš
AU  - Vujić, Zorica
AU  - Čudina, Olivera
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5458
AB  - The pathogenesis and progression of a various diseases, such as cancer, rheumatoid arthritis, autoimmune, cardiovascular and neurodegenerative diseases, are closely related to chronic inflammatory processes. ...
PB  - European Federation for Medicinal chemistry and Chemical biology (EFMC)
C3  - EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts
T1  - Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors
SP  - 154
EP  - 154
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5458
ER  - 

@conference{
author = "Bošković, Jelena and Dobričić, Vladimir and Nedeljković, Nikola and Nikolić, Miloš and Vujić, Zorica and Čudina, Olivera",
year = "2023",
abstract = "The pathogenesis and progression of a various diseases, such as cancer, rheumatoid arthritis, autoimmune, cardiovascular and neurodegenerative diseases, are closely related to chronic inflammatory processes. ...",
publisher = "European Federation for Medicinal chemistry and Chemical biology (EFMC)",
journal = "EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts",
title = "Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors",
pages = "154-154",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5458"
}

Bošković, J., Dobričić, V., Nedeljković, N., Nikolić, M., Vujić, Z.,& Čudina, O.. (2023). Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors. in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts
European Federation for Medicinal chemistry and Chemical biology (EFMC)., 154-154.
https://hdl.handle.net/21.15107/rcub_farfar_5458

Bošković J, Dobričić V, Nedeljković N, Nikolić M, Vujić Z, Čudina O. Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors. in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts. 2023;:154-154.
https://hdl.handle.net/21.15107/rcub_farfar_5458 .

Bošković, Jelena, Dobričić, Vladimir, Nedeljković, Nikola, Nikolić, Miloš, Vujić, Zorica, Čudina, Olivera, "Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors" in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts (2023):154-154,
https://hdl.handle.net/21.15107/rcub_farfar_5458 .

TY  - JOUR
AU  - Ivković, Branka
AU  - Milutinović, Ivana
AU  - Čudina, Olivera
AU  - Marković, Bojan
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4086
AB  - Gentamicin sulfate is a potent broad spectrum aminoglycoside antibiotic which is used against Gram- positive and Gram-negative bacteria. A simple, isocratic HPLC method for separation, identification and determination of gentamicin and parabens (methylparaben and propylparaben) was developed and validated. To our knowledge there is no report about simultaneous determination of those three ana- lytes in pharmaceutical products. The optimum chromatographic conditions were achieved on CN column with a mobile phase consisting of 0.15% triethylamine in 10 mM KH 2 PO4 aqueous solution (final pH 3.0 adjusted with H 3 PO 4 ) and methanol in the ratio 70:30 (v/v), providing selective quan- tification of analytes within 5 min. The method was successfully validated according to ICH guidelines acceptance criteria in terms of selectivity, linearity, accuracy, precision and robustness. The linearity of the method was proved in defined concentrations ranges for gentamicin (0.32–1.04 mg mL1 ), meth- ylparaben (0.0072–0.0234 mg mL1 ) and propylparaben (0.0008–0.0026 mg mL1 ). Relative standard deviations calculated for all analytes in precision testing were <2% (analysis repeatability) and <3% (intermediate precision). Recovery values were between 98.87% and 101.67%. Chromatographic pa- rameters are not significantly influenced by small variations of column temperature, pH and molarity of KH2 PO 4 . Finally, the method was successfully applied for quantitative determination of gentamicin and parabens in commercially available solution for injection. Proposed HPLC method is found to be promising in terms of simplicity, analysis times and non-use of derivatization and ion-pair agents.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben
VL  - 35
IS  - 1
SP  - 81
EP  - 87
DO  - 10.1556/1326.2022.00999
ER  - 

@article{
author = "Ivković, Branka and Milutinović, Ivana and Čudina, Olivera and Marković, Bojan",
year = "2023",
abstract = "Gentamicin sulfate is a potent broad spectrum aminoglycoside antibiotic which is used against Gram- positive and Gram-negative bacteria. A simple, isocratic HPLC method for separation, identification and determination of gentamicin and parabens (methylparaben and propylparaben) was developed and validated. To our knowledge there is no report about simultaneous determination of those three ana- lytes in pharmaceutical products. The optimum chromatographic conditions were achieved on CN column with a mobile phase consisting of 0.15% triethylamine in 10 mM KH 2 PO4 aqueous solution (final pH 3.0 adjusted with H 3 PO 4 ) and methanol in the ratio 70:30 (v/v), providing selective quan- tification of analytes within 5 min. The method was successfully validated according to ICH guidelines acceptance criteria in terms of selectivity, linearity, accuracy, precision and robustness. The linearity of the method was proved in defined concentrations ranges for gentamicin (0.32–1.04 mg mL1 ), meth- ylparaben (0.0072–0.0234 mg mL1 ) and propylparaben (0.0008–0.0026 mg mL1 ). Relative standard deviations calculated for all analytes in precision testing were <2% (analysis repeatability) and <3% (intermediate precision). Recovery values were between 98.87% and 101.67%. Chromatographic pa- rameters are not significantly influenced by small variations of column temperature, pH and molarity of KH2 PO 4 . Finally, the method was successfully applied for quantitative determination of gentamicin and parabens in commercially available solution for injection. Proposed HPLC method is found to be promising in terms of simplicity, analysis times and non-use of derivatization and ion-pair agents.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben",
volume = "35",
number = "1",
pages = "81-87",
doi = "10.1556/1326.2022.00999"
}

Ivković, B., Milutinović, I., Čudina, O.,& Marković, B.. (2023). A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben. in Acta Chromatographica
Akademiai Kiado ZRt.., 35(1), 81-87.
https://doi.org/10.1556/1326.2022.00999

Ivković B, Milutinović I, Čudina O, Marković B. A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben. in Acta Chromatographica. 2023;35(1):81-87.
doi:10.1556/1326.2022.00999 .

Ivković, Branka, Milutinović, Ivana, Čudina, Olivera, Marković, Bojan, "A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben" in Acta Chromatographica, 35, no. 1 (2023):81-87,
https://doi.org/10.1556/1326.2022.00999 . .

TY  - JOUR
AU  - Rupar, Jelena
AU  - Dobričić, Vladimir
AU  - Brborić, Jasmina
AU  - Čudina, Olivera
AU  - Aleksić, Mara
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4323
AB  - Electrochemical oxidation of newly synthesized acridine derivatives (ADs): PG, PA, EG and EA was studied using square wave voltammetry at a glassy carbon electrode. Oxidation occurs as an irreversible process for all ADs. The ADs interaction with DNA was investigated using multi-layer DNA electrochemical biosensor. The shift of dA peak in positive direction indicated that the type of interaction is most likely an intercalation. PG showed the widest range of concentration capable to interact with DNA (1 × 10−7 M − 2.5 × 10−4 M). Analysing [Formula presented] vs logcAD plots, the binding constants were determined. For the lowest PG concentrations, obtained K value close to 106 M−1 refers to strong binding. The values of K for PA may be classified as medium strength, while EG and EA showed low K values. Our results unequivocally showed that the characteristics of association complexes may vary depending on the concentration of the interacting substance. The negative ΔG value for all ADs, (- 21 to - 34 kJ mol−1), confirms the process spontaneity. The best result, indicating the most stable formed complex with DNA adsorbed at the electrode surface, showed PG when present in low concentration, order of 10−7 M. The intercalation of ADs into DNA was supported by molecular docking analysis.
PB  - Elsevier B.V.
T2  - Bioelectrochemistry
T1  - Square wave voltammetric study of interaction between 9-acridinyl amino acid derivatives and DNA
VL  - 149
DO  - 10.1016/j.bioelechem.2022.108323
ER  - 

@article{
author = "Rupar, Jelena and Dobričić, Vladimir and Brborić, Jasmina and Čudina, Olivera and Aleksić, Mara",
year = "2023",
abstract = "Electrochemical oxidation of newly synthesized acridine derivatives (ADs): PG, PA, EG and EA was studied using square wave voltammetry at a glassy carbon electrode. Oxidation occurs as an irreversible process for all ADs. The ADs interaction with DNA was investigated using multi-layer DNA electrochemical biosensor. The shift of dA peak in positive direction indicated that the type of interaction is most likely an intercalation. PG showed the widest range of concentration capable to interact with DNA (1 × 10−7 M − 2.5 × 10−4 M). Analysing [Formula presented] vs logcAD plots, the binding constants were determined. For the lowest PG concentrations, obtained K value close to 106 M−1 refers to strong binding. The values of K for PA may be classified as medium strength, while EG and EA showed low K values. Our results unequivocally showed that the characteristics of association complexes may vary depending on the concentration of the interacting substance. The negative ΔG value for all ADs, (- 21 to - 34 kJ mol−1), confirms the process spontaneity. The best result, indicating the most stable formed complex with DNA adsorbed at the electrode surface, showed PG when present in low concentration, order of 10−7 M. The intercalation of ADs into DNA was supported by molecular docking analysis.",
publisher = "Elsevier B.V.",
journal = "Bioelectrochemistry",
title = "Square wave voltammetric study of interaction between 9-acridinyl amino acid derivatives and DNA",
volume = "149",
doi = "10.1016/j.bioelechem.2022.108323"
}

Rupar, J., Dobričić, V., Brborić, J., Čudina, O.,& Aleksić, M.. (2023). Square wave voltammetric study of interaction between 9-acridinyl amino acid derivatives and DNA. in Bioelectrochemistry
Elsevier B.V.., 149.
https://doi.org/10.1016/j.bioelechem.2022.108323

Rupar J, Dobričić V, Brborić J, Čudina O, Aleksić M. Square wave voltammetric study of interaction between 9-acridinyl amino acid derivatives and DNA. in Bioelectrochemistry. 2023;149.
doi:10.1016/j.bioelechem.2022.108323 .

Rupar, Jelena, Dobričić, Vladimir, Brborić, Jasmina, Čudina, Olivera, Aleksić, Mara, "Square wave voltammetric study of interaction between 9-acridinyl amino acid derivatives and DNA" in Bioelectrochemistry, 149 (2023),
https://doi.org/10.1016/j.bioelechem.2022.108323 . .

TY  - CONF
AU  - Bošković, Jelena
AU  - Crevar, Milkica
AU  - Čudina, Olivera
AU  - Dobričić, Vladimir
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5453
AB  - The chronic inflammatory process is associated with the development and progression of many diseases such as cancer, arthritis, autoimmune diseases, etc. Dual COX-2 and 5-LOX inhibitors have been developed to provide more potent anti-inflammatory agents with a better safety profile [1].
Nineteen newly synthesised potential dual COX-2 and 5-LOX inhibitors [2] were selected and their retention properties were tested in different RP-HPLC systems. RP-HPLC analysis was performed using a C18, a cyano and an amino column. The mobile phases were binary combinations of acetonitrile and phosphate buffer (pH 5.5 and pH 7.4) as well as methanol and phosphate buffer (pH 5.5 and pH 7.4) in different ratios. The amino column proved to be inadequate as the tested compounds were not retained on it.
According to preliminary results, methanol was not suitable as an organic modifier in the mobile phase as the retention time of the compounds was increased several times compared to acetonitrile. Acetonitrile was
chosen as the organic modifier. The logarithmic values of the retention factors (logk) were calculated for each sample and plotted with the percentage of organic modifier in the mobile phase. The chromatography parameters logkw, a and ϕ0 were determined according to equation (1) and equation (2) (S-percentage of
organic modifier in the mobile phase).
Logk = logkw + aS (1)
ϕ0 = - logkw/a (2)
On C18 and cyano columns, seven compounds (1A, 1G, 1ME, 1PE, and 2D) had no retention properties, which is consistent with their very low logD values, while three (1F, 1H, and QSAR17) compounds were outlayers. Systems consisting of C18 and cyano columns (on both pH 5.5 and 7.4) showed good correlation coefficients between the chromatography parameters logkw, a, and ϕ0 and the logD values determined with MarvinSketch. The most suitable system consisted of a C18 column, acetonitrile, and phosphate buffer pH 7.4, as it had the highest correlation coefficient between the chromatography parameter logkw and the logD value (R2=0.9023) (3 compounds were discarded).
PB  - Aristotle University, Greece
PB  - Paul Ehrlich MedChem EuroPhD Network
C3  - MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts
T1  - Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis
SP  - 116
EP  - 116
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5453
ER  - 

@conference{
author = "Bošković, Jelena and Crevar, Milkica and Čudina, Olivera and Dobričić, Vladimir",
year = "2023",
abstract = "The chronic inflammatory process is associated with the development and progression of many diseases such as cancer, arthritis, autoimmune diseases, etc. Dual COX-2 and 5-LOX inhibitors have been developed to provide more potent anti-inflammatory agents with a better safety profile [1].
Nineteen newly synthesised potential dual COX-2 and 5-LOX inhibitors [2] were selected and their retention properties were tested in different RP-HPLC systems. RP-HPLC analysis was performed using a C18, a cyano and an amino column. The mobile phases were binary combinations of acetonitrile and phosphate buffer (pH 5.5 and pH 7.4) as well as methanol and phosphate buffer (pH 5.5 and pH 7.4) in different ratios. The amino column proved to be inadequate as the tested compounds were not retained on it.
According to preliminary results, methanol was not suitable as an organic modifier in the mobile phase as the retention time of the compounds was increased several times compared to acetonitrile. Acetonitrile was
chosen as the organic modifier. The logarithmic values of the retention factors (logk) were calculated for each sample and plotted with the percentage of organic modifier in the mobile phase. The chromatography parameters logkw, a and ϕ0 were determined according to equation (1) and equation (2) (S-percentage of
organic modifier in the mobile phase).
Logk = logkw + aS (1)
ϕ0 = - logkw/a (2)
On C18 and cyano columns, seven compounds (1A, 1G, 1ME, 1PE, and 2D) had no retention properties, which is consistent with their very low logD values, while three (1F, 1H, and QSAR17) compounds were outlayers. Systems consisting of C18 and cyano columns (on both pH 5.5 and 7.4) showed good correlation coefficients between the chromatography parameters logkw, a, and ϕ0 and the logD values determined with MarvinSketch. The most suitable system consisted of a C18 column, acetonitrile, and phosphate buffer pH 7.4, as it had the highest correlation coefficient between the chromatography parameter logkw and the logD value (R2=0.9023) (3 compounds were discarded).",
publisher = "Aristotle University, Greece, Paul Ehrlich MedChem EuroPhD Network",
journal = "MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts",
title = "Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis",
pages = "116-116",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5453"
}

Bošković, J., Crevar, M., Čudina, O.,& Dobričić, V.. (2023). Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis. in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts
Aristotle University, Greece., 116-116.
https://hdl.handle.net/21.15107/rcub_farfar_5453

Bošković J, Crevar M, Čudina O, Dobričić V. Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis. in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts. 2023;:116-116.
https://hdl.handle.net/21.15107/rcub_farfar_5453 .

Bošković, Jelena, Crevar, Milkica, Čudina, Olivera, Dobričić, Vladimir, "Estimation of lipophilicity of newly synthesized potential COX-2 and 5-LOX inhibitors using RP-HPLC analysis" in MedChem2023, XII Paul Ehrlich MedChem EuroPhD Network Symposium, Thessaloniki, Greece, July 16th - 18th, Book of Abstracts (2023):116-116,
https://hdl.handle.net/21.15107/rcub_farfar_5453 .

TY  - JOUR
AU  - Bošković, Jelena
AU  - Dobričić, Vladimir
AU  - Mihajlović, Marija
AU  - Kotur-Stevuljević, Jelena
AU  - Čudina, Olivera
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4755
AB  - Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1–13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and “type B hydroxamic acids” (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests.
The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors
VL  - 16
IS  - 4
DO  - https://doi.org/10.3390/ph16040549
ER  - 

@article{
author = "Bošković, Jelena and Dobričić, Vladimir and Mihajlović, Marija and Kotur-Stevuljević, Jelena and Čudina, Olivera",
year = "2023",
abstract = "Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1–13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and “type B hydroxamic acids” (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests.
The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors",
volume = "16",
number = "4",
doi = "https://doi.org/10.3390/ph16040549"
}

Bošković, J., Dobričić, V., Mihajlović, M., Kotur-Stevuljević, J.,& Čudina, O.. (2023). Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors. in Pharmaceuticals
MDPI., 16(4).
https://doi.org/https://doi.org/10.3390/ph16040549

Bošković J, Dobričić V, Mihajlović M, Kotur-Stevuljević J, Čudina O. Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors. in Pharmaceuticals. 2023;16(4).
doi:https://doi.org/10.3390/ph16040549 .

Bošković, Jelena, Dobričić, Vladimir, Mihajlović, Marija, Kotur-Stevuljević, Jelena, Čudina, Olivera, "Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors" in Pharmaceuticals, 16, no. 4 (2023),
https://doi.org/https://doi.org/10.3390/ph16040549 . .

TY  - CONF
AU  - Bošković, Jelena
AU  - Dobričić, Vladimir
AU  - Ružić, Dušan
AU  - Nikolić, Katarina
AU  - Čudina, Olivera
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5451
AB  - Inflammation is a part of immune system's response to harmful intrinsic and
extrinsic stimuli, such as infection or injury. It has an important role in progression of some diseases, such as cancer, arthritis, stroke [1]. It is considered that inhibition of COX 2 and 5 LOX pathways of production of inflammation mediators provides a new strategy for development of more effective anticancer drugs [2]. The aim of this study was designing of novel COX 2/5 LOX inhibitors with improved activity towards both enzymes using quantitative structure activity relationships (QSAR). QSAR modeling was applied on a literature data set consisting of 28 dual COX 2/5 LOX inhibitors and obtained pharmacophoric features were used in design of novel compounds. Regarding prediction of activity of novel COX 2 and 5 LOX inhibitors, two models were developed. Based on values of Q2 (0.53 (COX 2 model) and 0.71 (5 LOX model)) and R2 pred (0.85 (for both COX 2 and 5 LOX models)), developed models have good predictive ability and can be used for activity prediction of novel designed compounds.
Obtained values of r2m, r'2m, and r ̅2m were higher than 0.5 and Δr2m was lower than 0.2 indicating high predictive quality of developed models. Applicability domain (AD) was defined using Leverage approach and all compounds were inside the AD. In order to get more potent dual inhibitors of COX 2 and 5 LOX enzymes, compounds with high pIC50 values were chosen for design of novel compounds. As a result, 32 novel compounds were designed and according to predicted pIC50 values can be considered promising dual COX 2 and 5 LOX inhibitors.
PB  - Institut Químic de Sarrià - Universitat Ramon Llull (IQS-URL)
C3  - MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts
T1  - Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis
SP  - 57
EP  - 57
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5451
ER  - 

@conference{
author = "Bošković, Jelena and Dobričić, Vladimir and Ružić, Dušan and Nikolić, Katarina and Čudina, Olivera",
year = "2022",
abstract = "Inflammation is a part of immune system's response to harmful intrinsic and
extrinsic stimuli, such as infection or injury. It has an important role in progression of some diseases, such as cancer, arthritis, stroke [1]. It is considered that inhibition of COX 2 and 5 LOX pathways of production of inflammation mediators provides a new strategy for development of more effective anticancer drugs [2]. The aim of this study was designing of novel COX 2/5 LOX inhibitors with improved activity towards both enzymes using quantitative structure activity relationships (QSAR). QSAR modeling was applied on a literature data set consisting of 28 dual COX 2/5 LOX inhibitors and obtained pharmacophoric features were used in design of novel compounds. Regarding prediction of activity of novel COX 2 and 5 LOX inhibitors, two models were developed. Based on values of Q2 (0.53 (COX 2 model) and 0.71 (5 LOX model)) and R2 pred (0.85 (for both COX 2 and 5 LOX models)), developed models have good predictive ability and can be used for activity prediction of novel designed compounds.
Obtained values of r2m, r'2m, and r ̅2m were higher than 0.5 and Δr2m was lower than 0.2 indicating high predictive quality of developed models. Applicability domain (AD) was defined using Leverage approach and all compounds were inside the AD. In order to get more potent dual inhibitors of COX 2 and 5 LOX enzymes, compounds with high pIC50 values were chosen for design of novel compounds. As a result, 32 novel compounds were designed and according to predicted pIC50 values can be considered promising dual COX 2 and 5 LOX inhibitors.",
publisher = "Institut Químic de Sarrià - Universitat Ramon Llull (IQS-URL)",
journal = "MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts",
title = "Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis",
pages = "57-57",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5451"
}

Bošković, J., Dobričić, V., Ružić, D., Nikolić, K.,& Čudina, O.. (2022). Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis. in MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts
Institut Químic de Sarrià - Universitat Ramon Llull (IQS-URL)., 57-57.
https://hdl.handle.net/21.15107/rcub_farfar_5451

Bošković J, Dobričić V, Ružić D, Nikolić K, Čudina O. Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis. in MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts. 2022;:57-57.
https://hdl.handle.net/21.15107/rcub_farfar_5451 .

Bošković, Jelena, Dobričić, Vladimir, Ružić, Dušan, Nikolić, Katarina, Čudina, Olivera, "Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis" in MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts (2022):57-57,
https://hdl.handle.net/21.15107/rcub_farfar_5451 .

TY  - JOUR
AU  - Bošković, Jelena
AU  - Ružić, Dušan
AU  - Čudina, Olivera
AU  - Nikolić, Katarina
AU  - Dobričić, Vladimir
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5442
AB  - Background: Inflammation is a critical component of many disease progressions, such as malignancy, cardiovascular and rheumatic diseases. The inhibition of inflammatory mediators synthesis by modulation of cyclooxygenase (COX) and lipoxygenase (LOX) pathways provides challenging strategy for development of more effective drugs.

Objective: The aim of this study was to design dual COX-2 and 5-LOX inhibitors with iron-chelating properties using a combination of ligand-based (three-dimensional quantitative structure-activity relationship (3D-QSAR)) and structure-based (molecular docking) methods..

Methods: The 3D-QSAR analysis was applied on a literature dataset consisting of 28 dual COX-2 and 5- LOX inhibitors in Pentacle software. The quality of developed COX-2 and 5-LOX 3D-QSAR models were evaluated by internal and external validation methods. The molecular docking analysis was performed in GOLD software, while selected ADMET properties were predicted in ADMET predictor software.

Results: According to the molecular docking studies, the class of sulfohydroxamic acid analogues, previously designed by 3D-QSAR, were clustered as potential dual COX-2 and 5-LOX inhibitors with ironchelating properties. Based on the 3D-QSAR and molecular docking, 1j, 1g and 1l were selected as the most promising dual COX-2 and 5-LOX inhibitors. According to the in silico ADMET predictions, all compounds had ADMET_Risk score less than 7 and CYP_Risk score lower than 2.5. Designed compounds were not estimated as hERG inhibitors and 1j had improved intrinsic solubility (8.704) in comparison to the dataset compounds (0.411-7.946).

Conclusion: By combining 3D-QSAR and molecular docking, three compounds (1j, 1g and 1l) were selected as the most promising designed dual COX-2 and 5-LOX inhibitors, for which good activity, as well as favourable ADMET properties and toxicity, are expected.
PB  - Bentham Science Publishers
T2  - Letters in Drug Design & Discovery
T1  - Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods
VL  - 19
IS  - 4
SP  - 279
EP  - 292
DO  - 10.2174/1570180818666210714161908
ER  - 

@article{
author = "Bošković, Jelena and Ružić, Dušan and Čudina, Olivera and Nikolić, Katarina and Dobričić, Vladimir",
year = "2022",
abstract = "Background: Inflammation is a critical component of many disease progressions, such as malignancy, cardiovascular and rheumatic diseases. The inhibition of inflammatory mediators synthesis by modulation of cyclooxygenase (COX) and lipoxygenase (LOX) pathways provides challenging strategy for development of more effective drugs.

Objective: The aim of this study was to design dual COX-2 and 5-LOX inhibitors with iron-chelating properties using a combination of ligand-based (three-dimensional quantitative structure-activity relationship (3D-QSAR)) and structure-based (molecular docking) methods..

Methods: The 3D-QSAR analysis was applied on a literature dataset consisting of 28 dual COX-2 and 5- LOX inhibitors in Pentacle software. The quality of developed COX-2 and 5-LOX 3D-QSAR models were evaluated by internal and external validation methods. The molecular docking analysis was performed in GOLD software, while selected ADMET properties were predicted in ADMET predictor software.

Results: According to the molecular docking studies, the class of sulfohydroxamic acid analogues, previously designed by 3D-QSAR, were clustered as potential dual COX-2 and 5-LOX inhibitors with ironchelating properties. Based on the 3D-QSAR and molecular docking, 1j, 1g and 1l were selected as the most promising dual COX-2 and 5-LOX inhibitors. According to the in silico ADMET predictions, all compounds had ADMET_Risk score less than 7 and CYP_Risk score lower than 2.5. Designed compounds were not estimated as hERG inhibitors and 1j had improved intrinsic solubility (8.704) in comparison to the dataset compounds (0.411-7.946).

Conclusion: By combining 3D-QSAR and molecular docking, three compounds (1j, 1g and 1l) were selected as the most promising designed dual COX-2 and 5-LOX inhibitors, for which good activity, as well as favourable ADMET properties and toxicity, are expected.",
publisher = "Bentham Science Publishers",
journal = "Letters in Drug Design & Discovery",
title = "Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods",
volume = "19",
number = "4",
pages = "279-292",
doi = "10.2174/1570180818666210714161908"
}

Bošković, J., Ružić, D., Čudina, O., Nikolić, K.,& Dobričić, V.. (2022). Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods. in Letters in Drug Design & Discovery
Bentham Science Publishers., 19(4), 279-292.
https://doi.org/10.2174/1570180818666210714161908

Bošković J, Ružić D, Čudina O, Nikolić K, Dobričić V. Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods. in Letters in Drug Design & Discovery. 2022;19(4):279-292.
doi:10.2174/1570180818666210714161908 .

Bošković, Jelena, Ružić, Dušan, Čudina, Olivera, Nikolić, Katarina, Dobričić, Vladimir, "Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods" in Letters in Drug Design & Discovery, 19, no. 4 (2022):279-292,
https://doi.org/10.2174/1570180818666210714161908 . .

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Vukadinović, Dragana
AU  - Vladimirov, Sote
AU  - Čudina, Olivera
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4110
AB  - Eight 17b-carboxamide glucocorticoids with local anti-inflammatory activity were selected and their retention behavior tested in six RP-HPLC systems (I–VI). logkw, a, and 40 parameters were calculated and correlation with previously determined logPo/w values was examined. RP-HPLC system IV, which consisted of cyano column and methanol–water mobile phases (50:50, 60:40, 70:30, and 80:20, v/v), was selected as the most reliable for lipophilicity prediction and used for the analysis of chromatographic behavior of remaining fourteen 17b-carboxamide glucocorticoids. Quantitative structure-retention re- lationships analysis was performed and PLS(logkw) model was selected as the most statistically sig- nificant. On the basis of selected model and interpretation of corresponding descriptors, new derivatives with higher logkw values and higher expected lipophilicity were designed.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis
VL  - 34
IS  - 2
SP  - 130
EP  - 137
DO  - 10.1556/1326.2021.00893
ER  - 

@article{
author = "Dobričić, Vladimir and Bošković, Jelena and Vukadinović, Dragana and Vladimirov, Sote and Čudina, Olivera",
year = "2022",
abstract = "Eight 17b-carboxamide glucocorticoids with local anti-inflammatory activity were selected and their retention behavior tested in six RP-HPLC systems (I–VI). logkw, a, and 40 parameters were calculated and correlation with previously determined logPo/w values was examined. RP-HPLC system IV, which consisted of cyano column and methanol–water mobile phases (50:50, 60:40, 70:30, and 80:20, v/v), was selected as the most reliable for lipophilicity prediction and used for the analysis of chromatographic behavior of remaining fourteen 17b-carboxamide glucocorticoids. Quantitative structure-retention re- lationships analysis was performed and PLS(logkw) model was selected as the most statistically sig- nificant. On the basis of selected model and interpretation of corresponding descriptors, new derivatives with higher logkw values and higher expected lipophilicity were designed.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis",
volume = "34",
number = "2",
pages = "130-137",
doi = "10.1556/1326.2021.00893"
}

Dobričić, V., Bošković, J., Vukadinović, D., Vladimirov, S.,& Čudina, O.. (2022). Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis. in Acta Chromatographica
Akademiai Kiado ZRt.., 34(2), 130-137.
https://doi.org/10.1556/1326.2021.00893

Dobričić V, Bošković J, Vukadinović D, Vladimirov S, Čudina O. Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis. in Acta Chromatographica. 2022;34(2):130-137.
doi:10.1556/1326.2021.00893 .

Dobričić, Vladimir, Bošković, Jelena, Vukadinović, Dragana, Vladimirov, Sote, Čudina, Olivera, "Estimation of lipophilicity and design of new 17β-carboxamide glucocorticoids using RP-HPLC and quantitative structure-retention relationships analysis" in Acta Chromatographica, 34, no. 2 (2022):130-137,
https://doi.org/10.1556/1326.2021.00893 . .

TY  - CONF
AU  - Bošković, Jelena
AU  - Čudina, Olivera
AU  - Dobričić, Vladimir
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4595
AB  - Inflammatory mediators derived from arachidonic acid by the enzymes
cyclooxygenase (COX) and lipoxygenase (LOX) are involved in the pathogenesis of various
inflammatory diseases. Inhibition of the COX pathway is thought to lead to potentiation of
the LOX pathway, and inhibition of both pathways represents a rational approach to the
design and development of more effective and safer anti-inflammatory drugs (1). The aim of
this study was the synthesis and physico-chemical characterization of 1f, 1g and 1h
derivatives derived from a previously conducted 3D-QSAR study and molecular docking (2).
The sulfhydroxamic acid derivative 1f was synthesized in a two-step process. Sulfonyl
chloride was synthesized from commercially available sulfonic acid and thionyl chloride in
the presence of a catalytic amount of DMF. Sulfhydroxamic acid was further obtained from
previously synthesized sulfonyl chloride and hydroxylamine hydrochloride in the presence
of 10% NaHCO3 solution. Sulfhydroxamic acid derivatives, 1g and 1h were synthesized from
commercially available sulfonyl chlorides and hydroxylamine hydrochloride in the presence
of 10% NaHCO3 solution. The reaction mixtures were purified by liquid-liquid extraction and
preparative TLC to give derivatives 1f, 1g, 1h in yields: 26%, 53% and 63%. The structure
and purity of the synthesized compounds were confirmed by determination of the melting
points and spectroscopic techniques (ATR-FTIR, 1H-NMR, 13C-NMR, MS/MS). Based on a
previously conducted in silico study, the voluminous sulfhydroxamic group is responsible for
iron chelation within 5-LOX active center and for COX-2 selectivity, as COX-2 has wider side
pocket, so potent inhibition of COX-2 and 5-LOX enzymes is expected.
AB  - Inflamatorni medijatori koji nastaju iz arahidonske kiseline posredstvom enzima
ciklooksigenaze (COX) i lipooksigenaze (LOX) učestvuju u patogenezi brojnih inflamatornih
oboljenja. Smatra se da inhibicija COX puta dovodi do potenciranja LOX puta, te inhibicija oba
puta predstavlja racionalan pristup dizajniranja i razvoja novih, efikasnijih i bezbednijih
antiinflamatornih lekova (1). Cilj rada je bila sinteza i fizičko-hemijska karakterizacija
derivata 1f, 1g i 1h proisteklih iz prethodno sprovedene 3D-QSAR studije i molekulskog
docking-a (2). Derivat sulfhidroksamske kiseline 1f je sintetisan u dvostepenom postupku pri
čemu se najpre iz komercijalno dostupne sulfonske kiseline i tionil hlorida u prisustvu
katalitičke količine DMF dobija odgovarajući sulfonil hlorid. Odgovarajuća sulfhidroksamska
kiselina (1f) se dobija u drugom koraku iz prethodno sintetisanog sulfonil hlorida i
hidroksilamin-hidrohlorida u prisustvu 10% rastvora NaHCO3 . Derivati sulfhidroksamske
kiseline, 1g i 1h su sintetisani jednostepenim postupkom iz komercijalno dostupnih sulfonil
hlorida i hidroksilamin-hidrohlorida u prisustvu 10% rastvora NaHCO3 . Nakon postupka
sinteze jedinjenja su prečišćena tečno-tečnom ekstrakcijom i preparativnom TLC pri čemu se
dobijaju derivati 1f, 1g, 1h u prinosima 26%, 53% i 63%. Struktura i čistoća sintetisanih
jedinjenja je potvrđena određivanjem temperature topljenja i spektroskopskim (ATR-FTIR,
1 H-NMR, 13 C-NMR, MS/MS) tehnikama. Na osnovu prethodno sprovedene in silico studije,
voluminozni centar i sulfhidroksamska grupa sintetisanih derivata su odgovorni za COX-2
selektivnost zbog prisustva šireg vezivnog mesta unutar COX-2 enzima, dok
sulfhidroksamska grupa unutar 5-LOX enzima helira gvožđe aktivnog centra i inhibira enzim,
te se očekuje potentna dualna COX-2 i 5-LOX inhibitorna aktivnost sintetisanih derivata.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Synthesis and physicochemical characterization of three newly synthesized sulfhydroxamic acid derivatives as potential dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes
T1  - Sinteza i fizičko‐hemijska karakterizacija tri novosintetisana derivata sulfhidroksamske kiseline kao potencijalnih dualnih inhibitora enzima ciklooksigenaze‐2 i 5‐lipooksigenaze
VL  - 72
IS  - 4 suplement
SP  - S524
EP  - S525
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4595
ER  - 

@conference{
author = "Bošković, Jelena and Čudina, Olivera and Dobričić, Vladimir",
year = "2022",
abstract = "Inflammatory mediators derived from arachidonic acid by the enzymes
cyclooxygenase (COX) and lipoxygenase (LOX) are involved in the pathogenesis of various
inflammatory diseases. Inhibition of the COX pathway is thought to lead to potentiation of
the LOX pathway, and inhibition of both pathways represents a rational approach to the
design and development of more effective and safer anti-inflammatory drugs (1). The aim of
this study was the synthesis and physico-chemical characterization of 1f, 1g and 1h
derivatives derived from a previously conducted 3D-QSAR study and molecular docking (2).
The sulfhydroxamic acid derivative 1f was synthesized in a two-step process. Sulfonyl
chloride was synthesized from commercially available sulfonic acid and thionyl chloride in
the presence of a catalytic amount of DMF. Sulfhydroxamic acid was further obtained from
previously synthesized sulfonyl chloride and hydroxylamine hydrochloride in the presence
of 10% NaHCO3 solution. Sulfhydroxamic acid derivatives, 1g and 1h were synthesized from
commercially available sulfonyl chlorides and hydroxylamine hydrochloride in the presence
of 10% NaHCO3 solution. The reaction mixtures were purified by liquid-liquid extraction and
preparative TLC to give derivatives 1f, 1g, 1h in yields: 26%, 53% and 63%. The structure
and purity of the synthesized compounds were confirmed by determination of the melting
points and spectroscopic techniques (ATR-FTIR, 1H-NMR, 13C-NMR, MS/MS). Based on a
previously conducted in silico study, the voluminous sulfhydroxamic group is responsible for
iron chelation within 5-LOX active center and for COX-2 selectivity, as COX-2 has wider side
pocket, so potent inhibition of COX-2 and 5-LOX enzymes is expected., Inflamatorni medijatori koji nastaju iz arahidonske kiseline posredstvom enzima
ciklooksigenaze (COX) i lipooksigenaze (LOX) učestvuju u patogenezi brojnih inflamatornih
oboljenja. Smatra se da inhibicija COX puta dovodi do potenciranja LOX puta, te inhibicija oba
puta predstavlja racionalan pristup dizajniranja i razvoja novih, efikasnijih i bezbednijih
antiinflamatornih lekova (1). Cilj rada je bila sinteza i fizičko-hemijska karakterizacija
derivata 1f, 1g i 1h proisteklih iz prethodno sprovedene 3D-QSAR studije i molekulskog
docking-a (2). Derivat sulfhidroksamske kiseline 1f je sintetisan u dvostepenom postupku pri
čemu se najpre iz komercijalno dostupne sulfonske kiseline i tionil hlorida u prisustvu
katalitičke količine DMF dobija odgovarajući sulfonil hlorid. Odgovarajuća sulfhidroksamska
kiselina (1f) se dobija u drugom koraku iz prethodno sintetisanog sulfonil hlorida i
hidroksilamin-hidrohlorida u prisustvu 10% rastvora NaHCO3 . Derivati sulfhidroksamske
kiseline, 1g i 1h su sintetisani jednostepenim postupkom iz komercijalno dostupnih sulfonil
hlorida i hidroksilamin-hidrohlorida u prisustvu 10% rastvora NaHCO3 . Nakon postupka
sinteze jedinjenja su prečišćena tečno-tečnom ekstrakcijom i preparativnom TLC pri čemu se
dobijaju derivati 1f, 1g, 1h u prinosima 26%, 53% i 63%. Struktura i čistoća sintetisanih
jedinjenja je potvrđena određivanjem temperature topljenja i spektroskopskim (ATR-FTIR,
1 H-NMR, 13 C-NMR, MS/MS) tehnikama. Na osnovu prethodno sprovedene in silico studije,
voluminozni centar i sulfhidroksamska grupa sintetisanih derivata su odgovorni za COX-2
selektivnost zbog prisustva šireg vezivnog mesta unutar COX-2 enzima, dok
sulfhidroksamska grupa unutar 5-LOX enzima helira gvožđe aktivnog centra i inhibira enzim,
te se očekuje potentna dualna COX-2 i 5-LOX inhibitorna aktivnost sintetisanih derivata.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Synthesis and physicochemical characterization of three newly synthesized sulfhydroxamic acid derivatives as potential dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes, Sinteza i fizičko‐hemijska karakterizacija tri novosintetisana derivata sulfhidroksamske kiseline kao potencijalnih dualnih inhibitora enzima ciklooksigenaze‐2 i 5‐lipooksigenaze",
volume = "72",
number = "4 suplement",
pages = "S524-S525",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4595"
}

Bošković, J., Čudina, O.,& Dobričić, V.. (2022). Synthesis and physicochemical characterization of three newly synthesized sulfhydroxamic acid derivatives as potential dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S524-S525.
https://hdl.handle.net/21.15107/rcub_farfar_4595

Bošković J, Čudina O, Dobričić V. Synthesis and physicochemical characterization of three newly synthesized sulfhydroxamic acid derivatives as potential dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes. in Arhiv za farmaciju. 2022;72(4 suplement):S524-S525.
https://hdl.handle.net/21.15107/rcub_farfar_4595 .

Bošković, Jelena, Čudina, Olivera, Dobričić, Vladimir, "Synthesis and physicochemical characterization of three newly synthesized sulfhydroxamic acid derivatives as potential dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S524-S525,
https://hdl.handle.net/21.15107/rcub_farfar_4595 .

TY  - CONF
AU  - Zabelaj, Davor
AU  - Ivković, Branka
AU  - Čudina, Olivera
AU  - Brborić, Jasmina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4602
AB  - Flunixin is a non-steroidal anti-inflammatory drug, as well as an analgesic that has an
antipyretic effect. In veterinary medicine, it is used as salt flunixin meglumine. Flunixin
shows strong inhibition of the cyclooxygenase system involved in the development of
inflammation (1). The decrease in the production of certain inflammatory mediators explains
its analgesic, antipyretic and anti-inflammatory properties. A large number of methods have
been developed for the separation of flunixin meglumine and structurally related
compounds in pharmaceutical preparations, such as: thin layer chromatography, UV/VIS
spectroscopy, high pressure liquid chromatography and gas chromatography. The objective
of this work is to develop, optimize and validate a method for separating flunixin meglumine
and structurally related substances, in solution for injection. Optimal conditions were
achieved on a Agilent Zorbax Eclipse Plus C18 column (150×4.6 mm, 5 μm). The mobile
phase is a mixture of 0.1% (v/v) formic acid in water and methanol in a ratio of 40:60 (v/v).
The flow rate is 1.0 mL/min, the injection volume is 20 μL, the detection wavelength is 270
nm and the column temperature is 25°C. The following parameters were examined:
selectivity, linearity, precision, accuracy, detection limit, quantification limit, robustness and
stability of the solution (2). All these parameters were in line with the criteria for accepting
the results. Thereafter, the method was applied to determine the content of flunixin
meglumine and its impurities in the solution for injection, and the result was also in
accordance with the criteria for accepting the results.
AB  - Fluniksin je nesteroidni antiinflamatorni lek, kao i analgetik koji ima antipiretički
efekat. U veterinarskoj medicini se koristi u obliku soli fluniksin-meglumina. Fluniksin
pokazuje snažnu inhibiciju enzima ciklooksigenaze koji je uključen u nastanak inflamacije
(1). Smanjenjem produkcije određenih medijatora inflamacije objašnjavaju se njegova
analgetička, antipiretička i antiinflamatorna svojstva. Razvijen je veliki broj metoda za
odvajanje fluniksin meglumina i strukturno srodnih jedinjenja u farmaceutskim preparatima,
kao što su: tankoslojna hromatografija, UV/VIS spektroskopija, visokoefikasna tečna
hromatografija, gasna hromatografija. Cilj ovoga rada je razvoj, optimizacija i validacija
metode za razdvajanje i određivanje fluniksin-meglumina i strukturno sličnih jedinjenja, u
rastvoru za injekciju. Optimalni uslovi postignuti su na koloni Agilent Zorbax Eclipse Plus
C18 (150×4,6 mm, 5 μm). Mobilnu fazu činila je smeša 0,1% v/v rastvora mravlje kiseline u
vodi i metanola u odnosu 40:60 v/v. Protok mobilne faze je 1,0 mL/min, volumen injiciranja
20 μL, talasna dužina detekcije 270 nm i temperatura kolone 25°C. Ispitivani su sledeći
parametri: selektivnost, linearnost, preciznost, tačnost, limit detekcije, limit kvantifikacije,
robustnost i stabilnost rastvora (2). Dobijene vrednosti za ispitivane parametre su u skladu
sa kriterijumima prihvatljivosti. Validirana metoda je primenjena za određivanje sadržaja
fluniksin-meglumina i njegovih nečistoća u rastvoru za injekcije. Dobijeni rezultati
zadovoljavali su zahteve specifikacije.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use
T1  - Razvoj i validacija metode tečne hromatografije visokih performansi za određivanje fluniksin‐meglumina i njegovih nečistoća u preparatima za veterinarsku upotrebu
VL  - 72
IS  - 4 suplement
SP  - S540
EP  - S541
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4602
ER  - 

@conference{
author = "Zabelaj, Davor and Ivković, Branka and Čudina, Olivera and Brborić, Jasmina",
year = "2022",
abstract = "Flunixin is a non-steroidal anti-inflammatory drug, as well as an analgesic that has an
antipyretic effect. In veterinary medicine, it is used as salt flunixin meglumine. Flunixin
shows strong inhibition of the cyclooxygenase system involved in the development of
inflammation (1). The decrease in the production of certain inflammatory mediators explains
its analgesic, antipyretic and anti-inflammatory properties. A large number of methods have
been developed for the separation of flunixin meglumine and structurally related
compounds in pharmaceutical preparations, such as: thin layer chromatography, UV/VIS
spectroscopy, high pressure liquid chromatography and gas chromatography. The objective
of this work is to develop, optimize and validate a method for separating flunixin meglumine
and structurally related substances, in solution for injection. Optimal conditions were
achieved on a Agilent Zorbax Eclipse Plus C18 column (150×4.6 mm, 5 μm). The mobile
phase is a mixture of 0.1% (v/v) formic acid in water and methanol in a ratio of 40:60 (v/v).
The flow rate is 1.0 mL/min, the injection volume is 20 μL, the detection wavelength is 270
nm and the column temperature is 25°C. The following parameters were examined:
selectivity, linearity, precision, accuracy, detection limit, quantification limit, robustness and
stability of the solution (2). All these parameters were in line with the criteria for accepting
the results. Thereafter, the method was applied to determine the content of flunixin
meglumine and its impurities in the solution for injection, and the result was also in
accordance with the criteria for accepting the results., Fluniksin je nesteroidni antiinflamatorni lek, kao i analgetik koji ima antipiretički
efekat. U veterinarskoj medicini se koristi u obliku soli fluniksin-meglumina. Fluniksin
pokazuje snažnu inhibiciju enzima ciklooksigenaze koji je uključen u nastanak inflamacije
(1). Smanjenjem produkcije određenih medijatora inflamacije objašnjavaju se njegova
analgetička, antipiretička i antiinflamatorna svojstva. Razvijen je veliki broj metoda za
odvajanje fluniksin meglumina i strukturno srodnih jedinjenja u farmaceutskim preparatima,
kao što su: tankoslojna hromatografija, UV/VIS spektroskopija, visokoefikasna tečna
hromatografija, gasna hromatografija. Cilj ovoga rada je razvoj, optimizacija i validacija
metode za razdvajanje i određivanje fluniksin-meglumina i strukturno sličnih jedinjenja, u
rastvoru za injekciju. Optimalni uslovi postignuti su na koloni Agilent Zorbax Eclipse Plus
C18 (150×4,6 mm, 5 μm). Mobilnu fazu činila je smeša 0,1% v/v rastvora mravlje kiseline u
vodi i metanola u odnosu 40:60 v/v. Protok mobilne faze je 1,0 mL/min, volumen injiciranja
20 μL, talasna dužina detekcije 270 nm i temperatura kolone 25°C. Ispitivani su sledeći
parametri: selektivnost, linearnost, preciznost, tačnost, limit detekcije, limit kvantifikacije,
robustnost i stabilnost rastvora (2). Dobijene vrednosti za ispitivane parametre su u skladu
sa kriterijumima prihvatljivosti. Validirana metoda je primenjena za određivanje sadržaja
fluniksin-meglumina i njegovih nečistoća u rastvoru za injekcije. Dobijeni rezultati
zadovoljavali su zahteve specifikacije.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use, Razvoj i validacija metode tečne hromatografije visokih performansi za određivanje fluniksin‐meglumina i njegovih nečistoća u preparatima za veterinarsku upotrebu",
volume = "72",
number = "4 suplement",
pages = "S540-S541",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4602"
}

Zabelaj, D., Ivković, B., Čudina, O.,& Brborić, J.. (2022). Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S540-S541.
https://hdl.handle.net/21.15107/rcub_farfar_4602

Zabelaj D, Ivković B, Čudina O, Brborić J. Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use. in Arhiv za farmaciju. 2022;72(4 suplement):S540-S541.
https://hdl.handle.net/21.15107/rcub_farfar_4602 .

Zabelaj, Davor, Ivković, Branka, Čudina, Olivera, Brborić, Jasmina, "Development and validation of high-performance liquid chromatography method for determination of flunixin-meglumine and its impurities in preparations for veterinary use" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S540-S541,
https://hdl.handle.net/21.15107/rcub_farfar_4602 .

TY  - CONF
AU  - Bošković, Jelena
AU  - Ružić, Dušan
AU  - Čudina, Olivera
AU  - Nikolić, Katarina
AU  - Dobričić, Vladimir
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4939
AB  - Inflammation has an important function in progression of some diseases, such as cancer. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathways provides a rational strategy for development of more effective and safer anti-inflammatory drugs. It is assumed that compounds bearing sulfohydroxamic acid chelate catalytic iron inside 5-LOX enzyme and there are only few publications about performed molecular docking studies on these compounds. The main aim of our study was to establish valid and accurate molecular docking platform for future in silico screening and design of promising dual COX-2 and 5-LOX inhibitors with terminal sulfohydroxamic group. GOLD (Genetic Optimisation for Ligand Docking) software v.5.7 was used in order to predict the binding modes and docking poses of previously published dual COX-2 and 5-LOX inhibitors compounds in the active sites of COX-1, COX-2 and 5-LOX enzymes. Crystal structures were downloaded from the PDB website: 5WBE (for COX-1), 1CX2 (for COX-2) and 3O8Y (for 5-LOX). The first step was to investigate binding modes and docking poses of sulfohydroxamic analogues taken from literature, which expressed dual COX-2 and 5-LOX inhibitory activities and to establish correlation between experimentally obtained inhibitory activities and calculated scoring functions (ChemPLP for COX-1 and COX-2 enzymes, ASPFF for 5-LOX enzyme). Nine newly designed sulfohydroxamic analogues were docked into COX-1, COX-2 and 5-LOX enzymes. In the case of COX-2 enzyme, all designed compounds showed the same binding pattern as the co-crystalized ligand, SC-558, while no significant interactions were observed in the COX-1 enzyme. The compounds had lower ChemPLP scores when docked into COX-1 enzyme comparing to COX-2, which indicated good in silico predicted COX-2 selectivity. Obtained ASPFF and docking poses indicate that these compounds are potential 5-LOX chelating inhibitors. In this study, we developed valid molecular docking models to accelerate in silico identification and design of dual COX-2 and 5-LOX inhibitors bearing sulfohydroxamic acids.
C3  - Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021
T1  - Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking
SP  - 52
EP  - 52
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4939
ER  - 

@conference{
author = "Bošković, Jelena and Ružić, Dušan and Čudina, Olivera and Nikolić, Katarina and Dobričić, Vladimir",
year = "2021",
abstract = "Inflammation has an important function in progression of some diseases, such as cancer. Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathways provides a rational strategy for development of more effective and safer anti-inflammatory drugs. It is assumed that compounds bearing sulfohydroxamic acid chelate catalytic iron inside 5-LOX enzyme and there are only few publications about performed molecular docking studies on these compounds. The main aim of our study was to establish valid and accurate molecular docking platform for future in silico screening and design of promising dual COX-2 and 5-LOX inhibitors with terminal sulfohydroxamic group. GOLD (Genetic Optimisation for Ligand Docking) software v.5.7 was used in order to predict the binding modes and docking poses of previously published dual COX-2 and 5-LOX inhibitors compounds in the active sites of COX-1, COX-2 and 5-LOX enzymes. Crystal structures were downloaded from the PDB website: 5WBE (for COX-1), 1CX2 (for COX-2) and 3O8Y (for 5-LOX). The first step was to investigate binding modes and docking poses of sulfohydroxamic analogues taken from literature, which expressed dual COX-2 and 5-LOX inhibitory activities and to establish correlation between experimentally obtained inhibitory activities and calculated scoring functions (ChemPLP for COX-1 and COX-2 enzymes, ASPFF for 5-LOX enzyme). Nine newly designed sulfohydroxamic analogues were docked into COX-1, COX-2 and 5-LOX enzymes. In the case of COX-2 enzyme, all designed compounds showed the same binding pattern as the co-crystalized ligand, SC-558, while no significant interactions were observed in the COX-1 enzyme. The compounds had lower ChemPLP scores when docked into COX-1 enzyme comparing to COX-2, which indicated good in silico predicted COX-2 selectivity. Obtained ASPFF and docking poses indicate that these compounds are potential 5-LOX chelating inhibitors. In this study, we developed valid molecular docking models to accelerate in silico identification and design of dual COX-2 and 5-LOX inhibitors bearing sulfohydroxamic acids.",
journal = "Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021",
title = "Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking",
pages = "52-52",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4939"
}

Bošković, J., Ružić, D., Čudina, O., Nikolić, K.,& Dobričić, V.. (2021). Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking. in Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021, 52-52.
https://hdl.handle.net/21.15107/rcub_farfar_4939

Bošković J, Ružić D, Čudina O, Nikolić K, Dobričić V. Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking. in Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021. 2021;:52-52.
https://hdl.handle.net/21.15107/rcub_farfar_4939 .

Bošković, Jelena, Ružić, Dušan, Čudina, Olivera, Nikolić, Katarina, Dobričić, Vladimir, "Design of dual cyclooxygenase-2 and 5-lipoxygenase inhibitors with iron-chelating properties – molecular docking" in Paul Ehrlich (PE) Euro-PhD Network virtual meeting (PEVM2021), July 26th-28th, 2021 (2021):52-52,
https://hdl.handle.net/21.15107/rcub_farfar_4939 .

TY  - CONF
AU  - Rupar, Jelena
AU  - Aleksić, Mara
AU  - Dobričić, Vladimir
AU  - Čudina, Olivera
AU  - Brborić, Jasmina
AU  - Gavrilov, Nemanja
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5482
AB  - Oxidation of newly synthesized acridine derivatives was studied using cyclic voltammetry at glassy
carbon electrode. Oxidation occurs as irreversible, diffusion-controlled process at pH 4.6 for
compounds 1-3 and as adsorption controlled process for compound 4. The interaction between newly
synthesized acridine compounds (compounds 1-4) and dsDNA was studied using a multilayer dsDNA
biosensor applying square wave voltammetry. Peak current corresponding to deoxyadenosine
decreased after 30 minutes of interaction suggesting interaction with dsDNA.
PB  - Society of Physical Chemists of Serbia
C3  - Physical Chemistry 2021 (Proceedings), 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 20-24, 2021. Belgrade, Serbia
T1  - Electrochemical oxidation and interaction of newly synthesized acridine derivatives with DNA
VL  - I
SP  - 294
EP  - 297
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5482
ER  - 

@conference{
author = "Rupar, Jelena and Aleksić, Mara and Dobričić, Vladimir and Čudina, Olivera and Brborić, Jasmina and Gavrilov, Nemanja",
year = "2021",
abstract = "Oxidation of newly synthesized acridine derivatives was studied using cyclic voltammetry at glassy
carbon electrode. Oxidation occurs as irreversible, diffusion-controlled process at pH 4.6 for
compounds 1-3 and as adsorption controlled process for compound 4. The interaction between newly
synthesized acridine compounds (compounds 1-4) and dsDNA was studied using a multilayer dsDNA
biosensor applying square wave voltammetry. Peak current corresponding to deoxyadenosine
decreased after 30 minutes of interaction suggesting interaction with dsDNA.",
publisher = "Society of Physical Chemists of Serbia",
journal = "Physical Chemistry 2021 (Proceedings), 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 20-24, 2021. Belgrade, Serbia",
title = "Electrochemical oxidation and interaction of newly synthesized acridine derivatives with DNA",
volume = "I",
pages = "294-297",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5482"
}

Rupar, J., Aleksić, M., Dobričić, V., Čudina, O., Brborić, J.,& Gavrilov, N.. (2021). Electrochemical oxidation and interaction of newly synthesized acridine derivatives with DNA. in Physical Chemistry 2021 (Proceedings), 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 20-24, 2021. Belgrade, Serbia
Society of Physical Chemists of Serbia., I, 294-297.
https://hdl.handle.net/21.15107/rcub_farfar_5482

Rupar J, Aleksić M, Dobričić V, Čudina O, Brborić J, Gavrilov N. Electrochemical oxidation and interaction of newly synthesized acridine derivatives with DNA. in Physical Chemistry 2021 (Proceedings), 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 20-24, 2021. Belgrade, Serbia. 2021;I:294-297.
https://hdl.handle.net/21.15107/rcub_farfar_5482 .

Rupar, Jelena, Aleksić, Mara, Dobričić, Vladimir, Čudina, Olivera, Brborić, Jasmina, Gavrilov, Nemanja, "Electrochemical oxidation and interaction of newly synthesized acridine derivatives with DNA" in Physical Chemistry 2021 (Proceedings), 15th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 20-24, 2021. Belgrade, Serbia, I (2021):294-297,
https://hdl.handle.net/21.15107/rcub_farfar_5482 .

TY  - JOUR
AU  - Radan, Milica
AU  - Bošković, Jelena
AU  - Dobričić, Vladimir
AU  - Čudina, Olivera
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3950
AB  - Drug discovery and development is a very challenging, expensive and time-consuming
process. Impressive technological advances in computer sciences and molecular biology have
made it possible to use computer-aided drug design (CADD) methods in various stages of the
drug discovery and development pipeline. Nowadays, CADD presents an efficacious and
indispensable tool, widely used in medicinal chemistry, to lead rational drug design and synthesis
of novel compounds. In this article, an overview of commonly used CADD approaches from hit
identification to lead optimization was presented. Moreover, different aspects of design of multitarget ligands for neuropsychiatric and anti-inflammatory diseases were summarized. Apparently,
designing multi-target directed ligands for treatment of various complex diseases may offer better
efficacy, and fewer side effects. Antipsychotics that act through aminergic G protein-coupled
receptors (GPCRs), especially dopamine D2 and serotonin 5-HT2A receptors, are the best option
for treatment of various symptoms associated with neuropsychiatric disorders. Furthermore,
multi-target directed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors are also
a successful approach to aid the discovery of new anti-inflammatory drugs with fewer side effects.
Overall, employing CADD approaches in the process of rational drug design provides a great
opportunity for future development, allowing rapid identification of compounds with the optimal
polypharmacological profile.
AB  - Proces otkrića i razvoja lekova je veoma zahtevan, skup i dugotrajan. Veliki tehnološki napredak u molekularnoj biologiji i kompjuterskim naukama je omogućio primenu metoda kompjuterski potpomognutog dizajniranja lekova (CADD) u različitim fazama procesa otkrića i razvoja lekova. Danas CADD predstavlja efikasnu i nezamenljivu alatku, koja se široko koristi u medicinskoj hemiji za racionalni dizajn i sintezu novih jedinjenja. U ovom preglednom radu biće prikazani CADD pristupi koji se najčešće koriste od procesa identifikacije hit jedinjenja do optimizacije lead jedinjenja. Pored toga, biće predstavljeni različiti aspekti u dizajnu višeciljnih liganada za neuropsihijatrijske i inflamatorne bolesti. Pokazano je da su ova jedinjenja veoma efikasna u lečenju složenih bolesti zbog veće efikasnosti i manje neželjenih efekata koje izazivaju. Antipsihotici koji deluju preko aminergičnih G-protein spregnutih receptora (GPCR), posebno preko dopaminskih D2 i serotoninskih 5-HT2A receptora, predstavljaju najbolju opcija za lečenje različitih simptoma povezanih sa neuropsihijatrijskim poremećajima. Pored toga, dizajn i sinteza dualnih inhibitora ciklooksigenaze-2 (COX-2) i 5lipoksigenaze (5-LOX) takođe predstavlja uspešan pristup u otkrivanju novih antiinflamatornih lekova sa manje neželjenih efekata. Na kraju se može zaključiti da primena CADD metoda u procesu racionalnog dizajniranja lekova pruža značajnu priliku za dalji napredak jer omogućava brzu identifikaciju jedinjenja sa optimalnim polifarmakološkim profilom.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Current computer-aided drug design methodologies in discovery of novel drug candidates for neuropsychiatric and inflammatory diseases
T1  - Metode kompjuterski potpomognutog dizajniranja lekova u istraživanju novih potencijalnih terapeutika za neuropsihijatrijske i inflamatorne bolesti
VL  - 71
IS  - 4
SP  - 225
EP  - 256
DO  - 10.5937/arhfarm71-32523
ER  - 

@article{
author = "Radan, Milica and Bošković, Jelena and Dobričić, Vladimir and Čudina, Olivera and Nikolić, Katarina",
year = "2021",
abstract = "Drug discovery and development is a very challenging, expensive and time-consuming
process. Impressive technological advances in computer sciences and molecular biology have
made it possible to use computer-aided drug design (CADD) methods in various stages of the
drug discovery and development pipeline. Nowadays, CADD presents an efficacious and
indispensable tool, widely used in medicinal chemistry, to lead rational drug design and synthesis
of novel compounds. In this article, an overview of commonly used CADD approaches from hit
identification to lead optimization was presented. Moreover, different aspects of design of multitarget ligands for neuropsychiatric and anti-inflammatory diseases were summarized. Apparently,
designing multi-target directed ligands for treatment of various complex diseases may offer better
efficacy, and fewer side effects. Antipsychotics that act through aminergic G protein-coupled
receptors (GPCRs), especially dopamine D2 and serotonin 5-HT2A receptors, are the best option
for treatment of various symptoms associated with neuropsychiatric disorders. Furthermore,
multi-target directed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors are also
a successful approach to aid the discovery of new anti-inflammatory drugs with fewer side effects.
Overall, employing CADD approaches in the process of rational drug design provides a great
opportunity for future development, allowing rapid identification of compounds with the optimal
polypharmacological profile., Proces otkrića i razvoja lekova je veoma zahtevan, skup i dugotrajan. Veliki tehnološki napredak u molekularnoj biologiji i kompjuterskim naukama je omogućio primenu metoda kompjuterski potpomognutog dizajniranja lekova (CADD) u različitim fazama procesa otkrića i razvoja lekova. Danas CADD predstavlja efikasnu i nezamenljivu alatku, koja se široko koristi u medicinskoj hemiji za racionalni dizajn i sintezu novih jedinjenja. U ovom preglednom radu biće prikazani CADD pristupi koji se najčešće koriste od procesa identifikacije hit jedinjenja do optimizacije lead jedinjenja. Pored toga, biće predstavljeni različiti aspekti u dizajnu višeciljnih liganada za neuropsihijatrijske i inflamatorne bolesti. Pokazano je da su ova jedinjenja veoma efikasna u lečenju složenih bolesti zbog veće efikasnosti i manje neželjenih efekata koje izazivaju. Antipsihotici koji deluju preko aminergičnih G-protein spregnutih receptora (GPCR), posebno preko dopaminskih D2 i serotoninskih 5-HT2A receptora, predstavljaju najbolju opcija za lečenje različitih simptoma povezanih sa neuropsihijatrijskim poremećajima. Pored toga, dizajn i sinteza dualnih inhibitora ciklooksigenaze-2 (COX-2) i 5lipoksigenaze (5-LOX) takođe predstavlja uspešan pristup u otkrivanju novih antiinflamatornih lekova sa manje neželjenih efekata. Na kraju se može zaključiti da primena CADD metoda u procesu racionalnog dizajniranja lekova pruža značajnu priliku za dalji napredak jer omogućava brzu identifikaciju jedinjenja sa optimalnim polifarmakološkim profilom.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Current computer-aided drug design methodologies in discovery of novel drug candidates for neuropsychiatric and inflammatory diseases, Metode kompjuterski potpomognutog dizajniranja lekova u istraživanju novih potencijalnih terapeutika za neuropsihijatrijske i inflamatorne bolesti",
volume = "71",
number = "4",
pages = "225-256",
doi = "10.5937/arhfarm71-32523"
}

Radan, M., Bošković, J., Dobričić, V., Čudina, O.,& Nikolić, K.. (2021). Current computer-aided drug design methodologies in discovery of novel drug candidates for neuropsychiatric and inflammatory diseases. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 71(4), 225-256.
https://doi.org/10.5937/arhfarm71-32523

Radan M, Bošković J, Dobričić V, Čudina O, Nikolić K. Current computer-aided drug design methodologies in discovery of novel drug candidates for neuropsychiatric and inflammatory diseases. in Arhiv za farmaciju. 2021;71(4):225-256.
doi:10.5937/arhfarm71-32523 .

Radan, Milica, Bošković, Jelena, Dobričić, Vladimir, Čudina, Olivera, Nikolić, Katarina, "Current computer-aided drug design methodologies in discovery of novel drug candidates for neuropsychiatric and inflammatory diseases" in Arhiv za farmaciju, 71, no. 4 (2021):225-256,
https://doi.org/10.5937/arhfarm71-32523 . .

TY  - JOUR
AU  - Rupar, Jelena
AU  - Aleksić, Mara
AU  - Dobričić, Vladimir
AU  - Brborić, Jasmina
AU  - Čudina, Olivera
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3611
AB  - The electrochemical behavior of 9-chloroacridine (9Cl-A), a precursor molecule for synthesis of acridine derivatives with cytostatic activity, is a complex, pH-dependent, diffusion-controlled irreversible process. Oxidation of 9Cl-A initiates with the formation of a cation radical monomer, continues via the formation of a dimer subsequent oxidation to new cation radical. Reduction of 9Cl-A produces radical monomers which are stabilized by dimer formation. The investigation was performed using cyclic, differential pulse and square wave voltammetry at a glassy carbon electrode. The interaction between 9Cl-A and double-stranded DNA (dsDNA) was investigated using a multilayer dsDNA-electrochemical biosensor and 9Cl-A solutions from 1.0×10-7M (the lowest 9Cl-A concentration whose interaction with DNA was possible to detect) up to 1×10-4M. These allowed the binding constant, K=3.45×105M-1 and change in Gibbs free energy of the formed adsorbed complex to be calculated. Complex formation was a spontaneous process proceeding via 9Cl-A intercalation into dsDNA inducing structural changes. The intercalation of 9Cl-A into dsDNA was supported by molecular docking analysis. The combination of simple methodology and the use of biosensors to investigate DNA interactions is a powerful tool to offer insight into aspects of drug design during pharmaceutical development.
PB  - Elsevier B.V.
T2  - Bioelectrochemistry
T1  - An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA
VL  - 135
DO  - 10.1016/j.bioelechem.2020.107579
ER  - 

@article{
author = "Rupar, Jelena and Aleksić, Mara and Dobričić, Vladimir and Brborić, Jasmina and Čudina, Olivera",
year = "2020",
abstract = "The electrochemical behavior of 9-chloroacridine (9Cl-A), a precursor molecule for synthesis of acridine derivatives with cytostatic activity, is a complex, pH-dependent, diffusion-controlled irreversible process. Oxidation of 9Cl-A initiates with the formation of a cation radical monomer, continues via the formation of a dimer subsequent oxidation to new cation radical. Reduction of 9Cl-A produces radical monomers which are stabilized by dimer formation. The investigation was performed using cyclic, differential pulse and square wave voltammetry at a glassy carbon electrode. The interaction between 9Cl-A and double-stranded DNA (dsDNA) was investigated using a multilayer dsDNA-electrochemical biosensor and 9Cl-A solutions from 1.0×10-7M (the lowest 9Cl-A concentration whose interaction with DNA was possible to detect) up to 1×10-4M. These allowed the binding constant, K=3.45×105M-1 and change in Gibbs free energy of the formed adsorbed complex to be calculated. Complex formation was a spontaneous process proceeding via 9Cl-A intercalation into dsDNA inducing structural changes. The intercalation of 9Cl-A into dsDNA was supported by molecular docking analysis. The combination of simple methodology and the use of biosensors to investigate DNA interactions is a powerful tool to offer insight into aspects of drug design during pharmaceutical development.",
publisher = "Elsevier B.V.",
journal = "Bioelectrochemistry",
title = "An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA",
volume = "135",
doi = "10.1016/j.bioelechem.2020.107579"
}

Rupar, J., Aleksić, M., Dobričić, V., Brborić, J.,& Čudina, O.. (2020). An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA. in Bioelectrochemistry
Elsevier B.V.., 135.
https://doi.org/10.1016/j.bioelechem.2020.107579

Rupar J, Aleksić M, Dobričić V, Brborić J, Čudina O. An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA. in Bioelectrochemistry. 2020;135.
doi:10.1016/j.bioelechem.2020.107579 .

Rupar, Jelena, Aleksić, Mara, Dobričić, Vladimir, Brborić, Jasmina, Čudina, Olivera, "An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA" in Bioelectrochemistry, 135 (2020),
https://doi.org/10.1016/j.bioelechem.2020.107579 . .

TY  - JOUR
AU  - Rupar, Jelena
AU  - Dobričić, Vladimir
AU  - Grahovac, Jelena
AU  - Radulović, Siniša
AU  - Skok, Žiga
AU  - Ilaš, Janez
AU  - Aleksić, Mara
AU  - Brborić, Jasmina
AU  - Čudina, Olivera
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3606
AB  - A series of eleven 9-acridinyl amino acid derivatives were synthesized using a two-step procedure. Cytotoxicity was tested on the K562 and A549 cancer cell lines and normal diploid cell line MRC5 using the MTT assay. Compounds 6, 7, 8 and 9 were the most active, with IC50 values comparable to or lower than that of chemotherapeutic agent amsacrine. 8 and 9 were especially effective in the A549 cell line (IC50 ≈ 6 μM), which is of special interest since amsacrine is not sufficiently active in lung cancer patients. Cell cycle analysis revealed that 7 and 9 caused G2/M block, amsacrine caused arrest in the S phase, while 6 and 8 induced apoptotic cell death independently of the cell cycle regulation. In comparison to amsacrine, 6, 7, 8, and 9 showed similar inhibitory potential towards topoisomerase II, whereas only 7 showed DNA intercalation properties. In contrast to amsacrine, 6, 7, 8 and 9 showed a lack of toxicity towards unstimulated normal human leucocytes.
PB  - Royal Society of Chemistry
T2  - RSC Medicinal Chemistry
T1  - Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives
VL  - 11
IS  - 3
SP  - 378
EP  - 386
DO  - 10.1039/c9md00597h
DO  - 2-s2.0-85083014447
ER  - 

@article{
author = "Rupar, Jelena and Dobričić, Vladimir and Grahovac, Jelena and Radulović, Siniša and Skok, Žiga and Ilaš, Janez and Aleksić, Mara and Brborić, Jasmina and Čudina, Olivera",
year = "2020",
abstract = "A series of eleven 9-acridinyl amino acid derivatives were synthesized using a two-step procedure. Cytotoxicity was tested on the K562 and A549 cancer cell lines and normal diploid cell line MRC5 using the MTT assay. Compounds 6, 7, 8 and 9 were the most active, with IC50 values comparable to or lower than that of chemotherapeutic agent amsacrine. 8 and 9 were especially effective in the A549 cell line (IC50 ≈ 6 μM), which is of special interest since amsacrine is not sufficiently active in lung cancer patients. Cell cycle analysis revealed that 7 and 9 caused G2/M block, amsacrine caused arrest in the S phase, while 6 and 8 induced apoptotic cell death independently of the cell cycle regulation. In comparison to amsacrine, 6, 7, 8, and 9 showed similar inhibitory potential towards topoisomerase II, whereas only 7 showed DNA intercalation properties. In contrast to amsacrine, 6, 7, 8 and 9 showed a lack of toxicity towards unstimulated normal human leucocytes.",
publisher = "Royal Society of Chemistry",
journal = "RSC Medicinal Chemistry",
title = "Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives",
volume = "11",
number = "3",
pages = "378-386",
doi = "10.1039/c9md00597h, 2-s2.0-85083014447"
}

Rupar, J., Dobričić, V., Grahovac, J., Radulović, S., Skok, Ž., Ilaš, J., Aleksić, M., Brborić, J.,& Čudina, O.. (2020). Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives. in RSC Medicinal Chemistry
Royal Society of Chemistry., 11(3), 378-386.
https://doi.org/10.1039/c9md00597h

Rupar J, Dobričić V, Grahovac J, Radulović S, Skok Ž, Ilaš J, Aleksić M, Brborić J, Čudina O. Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives. in RSC Medicinal Chemistry. 2020;11(3):378-386.
doi:10.1039/c9md00597h .

Rupar, Jelena, Dobričić, Vladimir, Grahovac, Jelena, Radulović, Siniša, Skok, Žiga, Ilaš, Janez, Aleksić, Mara, Brborić, Jasmina, Čudina, Olivera, "Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives" in RSC Medicinal Chemistry, 11, no. 3 (2020):378-386,
https://doi.org/10.1039/c9md00597h . .

TY  - CONF
AU  - Dobričić, Vladimir
AU  - Oluić, Jelena
AU  - Nikolić, Katarina
AU  - Vučićević, Jelica
AU  - Gagić, Žarko
AU  - Filipić, Slavica
AU  - Agbaba, Danica
AU  - Čudina, Olivera
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5473
AB  - Multi-target compounds are designed to act on at least two targets in synergistic way, in order to produce stronger biological effect. The link
between cancer and inflammation has been intensively studied in last years and inhibition of both COX-2 and 5-LOX enzymes may be an
effective therapeutic approach for colon cancer treatment [1]. Acridines are known as DNA-topoisomerase II inhibitors. These compounds
intercalate into the DNA and inhibit topoisomerase II by their side chain. Recent studies showed additional activities of acridine derivatives,
depending on the side chain structure, such as inhibition of Src, MEK and VEGFR2 kinases [2,3]. Altered activity of PI3K/mTOR signaling pathway
is one of the most common aberrations found in various forms of neoplastic lesions. Dual inhibition of PI3K and mTOR represents a reasonably
attractive concept in potential cancer treatment [4]. In this paper, design of three groups of multi-target compounds with potential anticancer
activity is presented. Designed compounds are potential inhibitors of COX-2 and 5-LOX, DNA-topoisomerase II complex and kinases (Src, MEK
and VEGFR2), as well as dual inhibitors of mTOR and PI3K. A set of 27 compounds with published inhibitory activity on COX-2 and 5-LOX was
formed and two QSAR models, for both activities, were created in Pentacle program. On the basis of models’ interpretation, nine new
compounds were designed and activity on both targets predicted by developed models. Twenty-three acridine derivatives were designed and
their interactions with DNA-topoisomerase II complex, Src, MEK and VEGFR2 were tested using AutoDock Vina program. Nineteen designed
compounds bind to DNA similarly to inhibitor amsacrine and among them, ten derivatives show key binding interactions with tested kinases and
therefore possess potential to inhibit them. A dataset of eighty-five compounds with dual PI3K/mTOR inhibitory activities was formed,
divided into two groups based on their structural analogy and 3D-QSAR analysis of each group was performed in Pentacle program,
9
resulting in four QSAR models. On the basis of these results, new compounds were designed and further evaluated by use of molecular
docking, virtual screening and ADMET predictions. Finally, seven compounds were chosen as the most promising new dual mTOR/PI3K inhibitors.
PB  - COST Action 17104 (STRATAGEM)
C3  - STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy
T1  - Rational design of multi-target compounds with potential anticancer activity
SP  - 8
EP  - 9
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5473
ER  - 

@conference{
author = "Dobričić, Vladimir and Oluić, Jelena and Nikolić, Katarina and Vučićević, Jelica and Gagić, Žarko and Filipić, Slavica and Agbaba, Danica and Čudina, Olivera",
year = "2019",
abstract = "Multi-target compounds are designed to act on at least two targets in synergistic way, in order to produce stronger biological effect. The link
between cancer and inflammation has been intensively studied in last years and inhibition of both COX-2 and 5-LOX enzymes may be an
effective therapeutic approach for colon cancer treatment [1]. Acridines are known as DNA-topoisomerase II inhibitors. These compounds
intercalate into the DNA and inhibit topoisomerase II by their side chain. Recent studies showed additional activities of acridine derivatives,
depending on the side chain structure, such as inhibition of Src, MEK and VEGFR2 kinases [2,3]. Altered activity of PI3K/mTOR signaling pathway
is one of the most common aberrations found in various forms of neoplastic lesions. Dual inhibition of PI3K and mTOR represents a reasonably
attractive concept in potential cancer treatment [4]. In this paper, design of three groups of multi-target compounds with potential anticancer
activity is presented. Designed compounds are potential inhibitors of COX-2 and 5-LOX, DNA-topoisomerase II complex and kinases (Src, MEK
and VEGFR2), as well as dual inhibitors of mTOR and PI3K. A set of 27 compounds with published inhibitory activity on COX-2 and 5-LOX was
formed and two QSAR models, for both activities, were created in Pentacle program. On the basis of models’ interpretation, nine new
compounds were designed and activity on both targets predicted by developed models. Twenty-three acridine derivatives were designed and
their interactions with DNA-topoisomerase II complex, Src, MEK and VEGFR2 were tested using AutoDock Vina program. Nineteen designed
compounds bind to DNA similarly to inhibitor amsacrine and among them, ten derivatives show key binding interactions with tested kinases and
therefore possess potential to inhibit them. A dataset of eighty-five compounds with dual PI3K/mTOR inhibitory activities was formed,
divided into two groups based on their structural analogy and 3D-QSAR analysis of each group was performed in Pentacle program,
9
resulting in four QSAR models. On the basis of these results, new compounds were designed and further evaluated by use of molecular
docking, virtual screening and ADMET predictions. Finally, seven compounds were chosen as the most promising new dual mTOR/PI3K inhibitors.",
publisher = "COST Action 17104 (STRATAGEM)",
journal = "STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy",
title = "Rational design of multi-target compounds with potential anticancer activity",
pages = "8-9",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5473"
}

Dobričić, V., Oluić, J., Nikolić, K., Vučićević, J., Gagić, Ž., Filipić, S., Agbaba, D.,& Čudina, O.. (2019). Rational design of multi-target compounds with potential anticancer activity. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy
COST Action 17104 (STRATAGEM)., 8-9.
https://hdl.handle.net/21.15107/rcub_farfar_5473

Dobričić V, Oluić J, Nikolić K, Vučićević J, Gagić Ž, Filipić S, Agbaba D, Čudina O. Rational design of multi-target compounds with potential anticancer activity. in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy. 2019;:8-9.
https://hdl.handle.net/21.15107/rcub_farfar_5473 .

Dobričić, Vladimir, Oluić, Jelena, Nikolić, Katarina, Vučićević, Jelica, Gagić, Žarko, Filipić, Slavica, Agbaba, Danica, Čudina, Olivera, "Rational design of multi-target compounds with potential anticancer activity" in STRATAGEM CA17104, New Diagnostic and Therapeutic Tools against Multidrug-Resistant Tumors, first Working-Group Meeting, WG1 - WG4, 30 - 31. January 2019, Turin, Italy (2019):8-9,
https://hdl.handle.net/21.15107/rcub_farfar_5473 .

TY  - CONF
AU  - Dobričić, Vladimir
AU  - Savić, Jelena
AU  - Tomašič, Tihomir
AU  - Zidar, Nace
AU  - Peterlin Mašič, Lucija
AU  - Ilaš, Janez
AU  - Kikelj, Danijel
AU  - Čudina, Olivera
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5461
AB  - In this study, lipophilicity of twenty-three DNA gyrase and topoisomerase IV ATPase inhibitors was estimated at two
pH values (5.5 and 7.4) using reversed-phase high-performance liquid chromatography (RP-HPLC) [1,2]. Retention
behavior was tested on HP 1100 HPLC chromatograph, using column Zorbax Eclipse Plus C8 (150 X 4.6 mm, 5 µm
particle size). Mobile phase consisted of acetonitrile and phosphate buffer (pH was adjusted to 5.5 or 7.4). Each
compound was tested in four different ratios of acetonitrile and buffer (acetonitrile ranged from 20% to 65%). Column
temperature was 25 °C, flow rate 1 mL/min, injection volume 20 µL and detection was performed at 254 nm. For each
compound, capacity factor (k) was calculated and logk values were plotted against percentage of acetonitrile. Finally,
following chromatography parameters were calculated: logkw (y-axis intercept), a (slope) and ϕ0 (-logkw/a).
Derivatives with the highest lipophilicity were TEL-28 and NDL-20, whereas NZ97 had the lowest lipophilicity (at both
pH values, Figure 1). The majority of compounds possess similar or slightly different lipophilicities at both pH values,
but the highest differences were observed for TAZ-7, LMD-17 and NCH-4d, which could significantly affect their
biological properties (particularly gastrointestinal absorption, distribution and biological activity).
PB  - MuTaLig COST ACTION CA15135
C3  - Third WG Meeting CA15135, Cost Action CA15135, Februar 23 - 24. 2019. Pariz, Francuska
T1  - RP-HPLC evaluation of lipophilicity of a series of dual DNA gyrase and topoisomerase IV inhibitors
SP  - 32
EP  - 32
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5461
ER  - 

@conference{
author = "Dobričić, Vladimir and Savić, Jelena and Tomašič, Tihomir and Zidar, Nace and Peterlin Mašič, Lucija and Ilaš, Janez and Kikelj, Danijel and Čudina, Olivera",
year = "2019",
abstract = "In this study, lipophilicity of twenty-three DNA gyrase and topoisomerase IV ATPase inhibitors was estimated at two
pH values (5.5 and 7.4) using reversed-phase high-performance liquid chromatography (RP-HPLC) [1,2]. Retention
behavior was tested on HP 1100 HPLC chromatograph, using column Zorbax Eclipse Plus C8 (150 X 4.6 mm, 5 µm
particle size). Mobile phase consisted of acetonitrile and phosphate buffer (pH was adjusted to 5.5 or 7.4). Each
compound was tested in four different ratios of acetonitrile and buffer (acetonitrile ranged from 20% to 65%). Column
temperature was 25 °C, flow rate 1 mL/min, injection volume 20 µL and detection was performed at 254 nm. For each
compound, capacity factor (k) was calculated and logk values were plotted against percentage of acetonitrile. Finally,
following chromatography parameters were calculated: logkw (y-axis intercept), a (slope) and ϕ0 (-logkw/a).
Derivatives with the highest lipophilicity were TEL-28 and NDL-20, whereas NZ97 had the lowest lipophilicity (at both
pH values, Figure 1). The majority of compounds possess similar or slightly different lipophilicities at both pH values,
but the highest differences were observed for TAZ-7, LMD-17 and NCH-4d, which could significantly affect their
biological properties (particularly gastrointestinal absorption, distribution and biological activity).",
publisher = "MuTaLig COST ACTION CA15135",
journal = "Third WG Meeting CA15135, Cost Action CA15135, Februar 23 - 24. 2019. Pariz, Francuska",
title = "RP-HPLC evaluation of lipophilicity of a series of dual DNA gyrase and topoisomerase IV inhibitors",
pages = "32-32",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5461"
}

Dobričić, V., Savić, J., Tomašič, T., Zidar, N., Peterlin Mašič, L., Ilaš, J., Kikelj, D.,& Čudina, O.. (2019). RP-HPLC evaluation of lipophilicity of a series of dual DNA gyrase and topoisomerase IV inhibitors. in Third WG Meeting CA15135, Cost Action CA15135, Februar 23 - 24. 2019. Pariz, Francuska
MuTaLig COST ACTION CA15135., 32-32.
https://hdl.handle.net/21.15107/rcub_farfar_5461

Dobričić V, Savić J, Tomašič T, Zidar N, Peterlin Mašič L, Ilaš J, Kikelj D, Čudina O. RP-HPLC evaluation of lipophilicity of a series of dual DNA gyrase and topoisomerase IV inhibitors. in Third WG Meeting CA15135, Cost Action CA15135, Februar 23 - 24. 2019. Pariz, Francuska. 2019;:32-32.
https://hdl.handle.net/21.15107/rcub_farfar_5461 .

Dobričić, Vladimir, Savić, Jelena, Tomašič, Tihomir, Zidar, Nace, Peterlin Mašič, Lucija, Ilaš, Janez, Kikelj, Danijel, Čudina, Olivera, "RP-HPLC evaluation of lipophilicity of a series of dual DNA gyrase and topoisomerase IV inhibitors" in Third WG Meeting CA15135, Cost Action CA15135, Februar 23 - 24. 2019. Pariz, Francuska (2019):32-32,
https://hdl.handle.net/21.15107/rcub_farfar_5461 .

TY  - JOUR
AU  - Ivković, Branka
AU  - Brborić, Jasmina
AU  - Dobričić, Vladimir
AU  - Čudina, Olivera
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3355
AB  - A simple and convenient reversed-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous separation, identification, and determination of sodium metabisulfite and sodium benzoate in pharmaceutical formulation has been developed and validated. Chromatographic separation was achieved on RP column Zorbax Extend C-18 (150 x 4.6 mm i.d., 3.5 mu m particles), and mixture of 0.1% phosphoric acid and acetonitrile in the ratio 62: 38 (v/v) was used as a mobile phase. The flow rate was set at 1.0 mL/min with detection wavelength of 275 nm. The method was successfully validated according to International Conference on Harmonization (ICH) guidelines acceptance criteria. The method is selective, as no interferences were observed at retention times corresponding to these analytes. Results of regression analyses (r) and statistical insignificance of calibration curve intercepts (p) proved linearity of the method in defined concentration ranges for sodium metabisulfite and sodium benzoate (0.05-0.15 mg/mL). Relative standard deviations calculated for both analytes in precision testing were below the limits defined for active pharmaceutical ingredients (analysis repeatability:  lt  2%; intermediate precision:  lt  3%). Recovery values were between 98.16% and 101.94%. According to results of robustness testing, chromatographic parameters are not significantly influenced by small variation of acetonitrile content in mobile phase, column temperature, and flow rate. Finally, the method was applied for quantitative determination of investigated preservatives in real sample analysis.
PB  - Akademiai Kiado Zrt, Budapest
T2  - Acta Chromatographica
T1  - Development and Validation of a New Isocratic RP-HPLC Method for Simultaneous Determination of Sodium Metabisulfite and Sodium Benzoate in Pharmaceutical Formulation
VL  - 31
IS  - 2
SP  - 133
EP  - 137
DO  - 10.1556/1326.2017.00404
ER  - 

@article{
author = "Ivković, Branka and Brborić, Jasmina and Dobričić, Vladimir and Čudina, Olivera",
year = "2019",
abstract = "A simple and convenient reversed-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous separation, identification, and determination of sodium metabisulfite and sodium benzoate in pharmaceutical formulation has been developed and validated. Chromatographic separation was achieved on RP column Zorbax Extend C-18 (150 x 4.6 mm i.d., 3.5 mu m particles), and mixture of 0.1% phosphoric acid and acetonitrile in the ratio 62: 38 (v/v) was used as a mobile phase. The flow rate was set at 1.0 mL/min with detection wavelength of 275 nm. The method was successfully validated according to International Conference on Harmonization (ICH) guidelines acceptance criteria. The method is selective, as no interferences were observed at retention times corresponding to these analytes. Results of regression analyses (r) and statistical insignificance of calibration curve intercepts (p) proved linearity of the method in defined concentration ranges for sodium metabisulfite and sodium benzoate (0.05-0.15 mg/mL). Relative standard deviations calculated for both analytes in precision testing were below the limits defined for active pharmaceutical ingredients (analysis repeatability:  lt  2%; intermediate precision:  lt  3%). Recovery values were between 98.16% and 101.94%. According to results of robustness testing, chromatographic parameters are not significantly influenced by small variation of acetonitrile content in mobile phase, column temperature, and flow rate. Finally, the method was applied for quantitative determination of investigated preservatives in real sample analysis.",
publisher = "Akademiai Kiado Zrt, Budapest",
journal = "Acta Chromatographica",
title = "Development and Validation of a New Isocratic RP-HPLC Method for Simultaneous Determination of Sodium Metabisulfite and Sodium Benzoate in Pharmaceutical Formulation",
volume = "31",
number = "2",
pages = "133-137",
doi = "10.1556/1326.2017.00404"
}

Ivković, B., Brborić, J., Dobričić, V.,& Čudina, O.. (2019). Development and Validation of a New Isocratic RP-HPLC Method for Simultaneous Determination of Sodium Metabisulfite and Sodium Benzoate in Pharmaceutical Formulation. in Acta Chromatographica
Akademiai Kiado Zrt, Budapest., 31(2), 133-137.
https://doi.org/10.1556/1326.2017.00404

Ivković B, Brborić J, Dobričić V, Čudina O. Development and Validation of a New Isocratic RP-HPLC Method for Simultaneous Determination of Sodium Metabisulfite and Sodium Benzoate in Pharmaceutical Formulation. in Acta Chromatographica. 2019;31(2):133-137.
doi:10.1556/1326.2017.00404 .

Ivković, Branka, Brborić, Jasmina, Dobričić, Vladimir, Čudina, Olivera, "Development and Validation of a New Isocratic RP-HPLC Method for Simultaneous Determination of Sodium Metabisulfite and Sodium Benzoate in Pharmaceutical Formulation" in Acta Chromatographica, 31, no. 2 (2019):133-137,
https://doi.org/10.1556/1326.2017.00404 . .

TY  - CONF
AU  - Dobričić, Vladimir
AU  - Savić, Jelena
AU  - Tubić, Biljana
AU  - Nikolić, Katarina
AU  - Brborić, Jasmina
AU  - Marković, Bojan
AU  - Čudina, Olivera
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5457
AB  - PAMPA (Parallel Artificial Membrane Permeability Assay) je brza i jednostavna in
vitro tehnika za procenu gastrointestinalne apsorpcije. Zasniva se na pasivnoj difuziji
ispitivanih supstanci kroz veštačku membranu koja simulira gastrointestinalni trakt.
QSPR (Quantitative Structure‐ Permeability Relationship Analysis) povezuje rezultate
PAMPA testa sa fizičko‐hemijskim osobinama ispitivanih jedinjenja, na osnovu čega je
moguć dizajn novih derivata sa poboljšanom apsorpcijom. Cilj rada je procena
gastrointestinalne apsorpcije trinaest β‐hidroksi‐β‐arilalkanskih kiselina sa
antiinflamatornom aktivnošću i četrnaest derivata 1,2‐etandiamina i 1,3‐
propandiamina sa antiproliferativnom aktivnošću primenom PAMPA testa, kao i dizajn
novih jedinjenja na osnovu QSPR analiza.
Gastrointestinalna apsorpcija je procenjena na hidrofobnim PVDF PAMPA
pločama, impregniranim 1% rastvorom lecitina jajeta u dodekanu (w/v). Molekulski
deskriptori ispitivanih jedinjenja su izračunati u programu Dragon i pomoću platforme
ChemDes. QSPR modeli su napravljeni u programima Simca 12+ P i STATISTICA.
Za sva ispitivana jedinjenja određeni su koeficijenti permeabilnosti (Papp)
primenom PAMPA testa, a za formiranje QSPR modela izračunati su i negativni
logaritmi ovih koeficijenata (‐logP app). Izdvojene su β‐hidroksi‐β‐arilalkanske kiseline
(1C, 1B i 2C), kao i derivati 1,2‐etandiamina i 1,3‐propandiamina (DM‐EDCP, EDCP i
DM‐PDCP) sa najvećom permeabilnošću kroz PAMPA membranu. Formirani su ANN‐,
MLR‐, PLS‐ i SVM‐QSPR modeli, pri čemu su najpouzdaniji modeli za predviđanje
permeabilnosti MLR(‐logP app) (za β‐hidroksi‐β‐arilalkanske kiseline), odnosno
PLS(‐logP app) (za derivate 1,2‐etandiamina i 1,3‐propandiamina). Na osnovu
deskriptora koji formiraju izdvojene modele predložene su strukturne promene koje bi
trebalo da poboljšaju permeabilnost kroz PAMPA veštačku membranu i
gastrointestinalnu apsorpciju.
Primenom PAMPA tehnike procenjena je gastrointestinalna apsorpcija trinaest
β‐hidroksi‐β‐arilalkanskih kiselina, kao i četrnaest derivata 1,2‐etandiamina i 1,3‐
propandiamina. Izdvojeni su derivati sa najvećom permeabilnošću i formirani su QSPR
modeli. Analizom najpouzdanijih modela, predložene su strukturne promene i
dizajnirani su novi derivati od kojih se može očekivati bolja gastrointestinalna
apsorpcija.
AB  - PAMPA (Parallel Artificial Membrane Permeability Assay) is a fast and simple in vitro technique used for the evaluation of gastrointestinal absorption. It is based on passive diffusion of tested substances through artificial membrane which simulates gastrointestinal tract. QSPR (Quantitative Structure‐Permeability Relationship Analysis) relates PAMPA results to physico‐chemical properties of tested compounds, which can be used for design of new derivatives with improved absorption. The aim of this work was evaluation of gastrointestinal absorption of thirteen β‐hydroxy‐β‐ arylalkanoic acids with antiinflammatory activity and fourteen derivatives of 1,2‐ ethanediamine and 1,3‐propanediamine with antiproliferative activity using PAMPA, as well as design of novel derivatives on the basis of QSPR analyses. Gastrointestinal absorption was evaluated using hydrophobic PAMPA plates impregnated with 1% egg lecithin solution in dodecane (w/v). Molecular descriptors of tested compounds were calculated using Dragon software and ChemDes platform. QSPR models were created in Simca 12+P and STATISTICA programs. Permeability coefficients (Papp) of all tested compounds were determined using PAMPA, whereas for QSPR modelling negative logarithms of these coefficients (‐logPapp) were calculated. β‐hydroxy‐β‐arylalkanoic acids (1C, 1B and 2C), as well as derivatives of 1,2‐ethanediamine and 1,3‐propanediamine (DM‐EDCP, EDCP and DM‐PDCP) with the highest PAMPA permeability were underlined. ANN‐, MLR‐, PLS‐ and SVM‐QSPR models were created, and the most reliable for permeability prediction were MLR(‐ logPapp) (β‐hydroxy‐β‐arylalkanoic acids) and PLS(‐logPapp) (derivatives of 1,2‐ ethanediamine and 1,3‐propanediamine). On the basis of descriptors that form selected models, structural modifications that should improve PAMPA permeability and gastrointestinal absorption were proposed. Gastrointestinal absorption of thirteen β‐hydroxy‐β‐arylalkanoic acids and fourteen derivatives of 1,2‐ethanediamine and 1,3‐propanediamine was evaluated using PAMPA technique. Derivatives with the highest permeability were underlined and QSPR models were created. After the analysis of the most reliable models, structural modifications were proposed and new derivatives with better expected gastrointestinal absorption were designed.
PB  - Savez farmaceutskih udruženja Srbije
C3  - Arhiv za farmaciju
T1  - Primena PAMPA tehnike i QSPR analize u proceni gastrointestinalne apsorpcije i dizajniranju novih biološki aktivnih jedinjenja
T1  - Application of PAMPA technique and QSPR analysis in the evaluation of gastrointestinal absorption and design of new biologically active compounds
VL  - 68
IS  - 2
SP  - 112
EP  - 113
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5457
ER  - 

@conference{
author = "Dobričić, Vladimir and Savić, Jelena and Tubić, Biljana and Nikolić, Katarina and Brborić, Jasmina and Marković, Bojan and Čudina, Olivera",
year = "2018",
abstract = "PAMPA (Parallel Artificial Membrane Permeability Assay) je brza i jednostavna in
vitro tehnika za procenu gastrointestinalne apsorpcije. Zasniva se na pasivnoj difuziji
ispitivanih supstanci kroz veštačku membranu koja simulira gastrointestinalni trakt.
QSPR (Quantitative Structure‐ Permeability Relationship Analysis) povezuje rezultate
PAMPA testa sa fizičko‐hemijskim osobinama ispitivanih jedinjenja, na osnovu čega je
moguć dizajn novih derivata sa poboljšanom apsorpcijom. Cilj rada je procena
gastrointestinalne apsorpcije trinaest β‐hidroksi‐β‐arilalkanskih kiselina sa
antiinflamatornom aktivnošću i četrnaest derivata 1,2‐etandiamina i 1,3‐
propandiamina sa antiproliferativnom aktivnošću primenom PAMPA testa, kao i dizajn
novih jedinjenja na osnovu QSPR analiza.
Gastrointestinalna apsorpcija je procenjena na hidrofobnim PVDF PAMPA
pločama, impregniranim 1% rastvorom lecitina jajeta u dodekanu (w/v). Molekulski
deskriptori ispitivanih jedinjenja su izračunati u programu Dragon i pomoću platforme
ChemDes. QSPR modeli su napravljeni u programima Simca 12+ P i STATISTICA.
Za sva ispitivana jedinjenja određeni su koeficijenti permeabilnosti (Papp)
primenom PAMPA testa, a za formiranje QSPR modela izračunati su i negativni
logaritmi ovih koeficijenata (‐logP app). Izdvojene su β‐hidroksi‐β‐arilalkanske kiseline
(1C, 1B i 2C), kao i derivati 1,2‐etandiamina i 1,3‐propandiamina (DM‐EDCP, EDCP i
DM‐PDCP) sa najvećom permeabilnošću kroz PAMPA membranu. Formirani su ANN‐,
MLR‐, PLS‐ i SVM‐QSPR modeli, pri čemu su najpouzdaniji modeli za predviđanje
permeabilnosti MLR(‐logP app) (za β‐hidroksi‐β‐arilalkanske kiseline), odnosno
PLS(‐logP app) (za derivate 1,2‐etandiamina i 1,3‐propandiamina). Na osnovu
deskriptora koji formiraju izdvojene modele predložene su strukturne promene koje bi
trebalo da poboljšaju permeabilnost kroz PAMPA veštačku membranu i
gastrointestinalnu apsorpciju.
Primenom PAMPA tehnike procenjena je gastrointestinalna apsorpcija trinaest
β‐hidroksi‐β‐arilalkanskih kiselina, kao i četrnaest derivata 1,2‐etandiamina i 1,3‐
propandiamina. Izdvojeni su derivati sa najvećom permeabilnošću i formirani su QSPR
modeli. Analizom najpouzdanijih modela, predložene su strukturne promene i
dizajnirani su novi derivati od kojih se može očekivati bolja gastrointestinalna
apsorpcija., PAMPA (Parallel Artificial Membrane Permeability Assay) is a fast and simple in vitro technique used for the evaluation of gastrointestinal absorption. It is based on passive diffusion of tested substances through artificial membrane which simulates gastrointestinal tract. QSPR (Quantitative Structure‐Permeability Relationship Analysis) relates PAMPA results to physico‐chemical properties of tested compounds, which can be used for design of new derivatives with improved absorption. The aim of this work was evaluation of gastrointestinal absorption of thirteen β‐hydroxy‐β‐ arylalkanoic acids with antiinflammatory activity and fourteen derivatives of 1,2‐ ethanediamine and 1,3‐propanediamine with antiproliferative activity using PAMPA, as well as design of novel derivatives on the basis of QSPR analyses. Gastrointestinal absorption was evaluated using hydrophobic PAMPA plates impregnated with 1% egg lecithin solution in dodecane (w/v). Molecular descriptors of tested compounds were calculated using Dragon software and ChemDes platform. QSPR models were created in Simca 12+P and STATISTICA programs. Permeability coefficients (Papp) of all tested compounds were determined using PAMPA, whereas for QSPR modelling negative logarithms of these coefficients (‐logPapp) were calculated. β‐hydroxy‐β‐arylalkanoic acids (1C, 1B and 2C), as well as derivatives of 1,2‐ethanediamine and 1,3‐propanediamine (DM‐EDCP, EDCP and DM‐PDCP) with the highest PAMPA permeability were underlined. ANN‐, MLR‐, PLS‐ and SVM‐QSPR models were created, and the most reliable for permeability prediction were MLR(‐ logPapp) (β‐hydroxy‐β‐arylalkanoic acids) and PLS(‐logPapp) (derivatives of 1,2‐ ethanediamine and 1,3‐propanediamine). On the basis of descriptors that form selected models, structural modifications that should improve PAMPA permeability and gastrointestinal absorption were proposed. Gastrointestinal absorption of thirteen β‐hydroxy‐β‐arylalkanoic acids and fourteen derivatives of 1,2‐ethanediamine and 1,3‐propanediamine was evaluated using PAMPA technique. Derivatives with the highest permeability were underlined and QSPR models were created. After the analysis of the most reliable models, structural modifications were proposed and new derivatives with better expected gastrointestinal absorption were designed.",
publisher = "Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Primena PAMPA tehnike i QSPR analize u proceni gastrointestinalne apsorpcije i dizajniranju novih biološki aktivnih jedinjenja, Application of PAMPA technique and QSPR analysis in the evaluation of gastrointestinal absorption and design of new biologically active compounds",
volume = "68",
number = "2",
pages = "112-113",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5457"
}

Dobričić, V., Savić, J., Tubić, B., Nikolić, K., Brborić, J., Marković, B.,& Čudina, O.. (2018). Primena PAMPA tehnike i QSPR analize u proceni gastrointestinalne apsorpcije i dizajniranju novih biološki aktivnih jedinjenja. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije., 68(2), 112-113.
https://hdl.handle.net/21.15107/rcub_farfar_5457

Dobričić V, Savić J, Tubić B, Nikolić K, Brborić J, Marković B, Čudina O. Primena PAMPA tehnike i QSPR analize u proceni gastrointestinalne apsorpcije i dizajniranju novih biološki aktivnih jedinjenja. in Arhiv za farmaciju. 2018;68(2):112-113.
https://hdl.handle.net/21.15107/rcub_farfar_5457 .

Dobričić, Vladimir, Savić, Jelena, Tubić, Biljana, Nikolić, Katarina, Brborić, Jasmina, Marković, Bojan, Čudina, Olivera, "Primena PAMPA tehnike i QSPR analize u proceni gastrointestinalne apsorpcije i dizajniranju novih biološki aktivnih jedinjenja" in Arhiv za farmaciju, 68, no. 2 (2018):112-113,
https://hdl.handle.net/21.15107/rcub_farfar_5457 .

TY  - CONF
AU  - Bošković, Jelena
AU  - Marković, Jelena
AU  - Dobričić, Vladimir
AU  - Čudina, Olivera
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5454
AB  - Amidi ili estri kortienske kiseline metilprednizolona predstavljaju potencijalne
soft glukokortikoide sa manje izraženim neželjenim efektima u odnosu na
konvencionalne glukokortikoide. Retencija i permeabilnost su važne osobine soft
glukokortikoida za primenu na kožu koje mogu značajno uticati na njihovu aktivnost i
pojavu neželjenih efekata. Jedna od in vitro metoda koja se najčešće koristi za procenu
ovih osobina je PAMPA (Parallel Artificial Membrane Permeability Assay). Cilj ovog
rada je procena permeabilnosti i retencije u koži pet amida (MPMA, MPMAB, MPMAIB,
MPMGB i MPPA) i jednog tioestra (MPEMP) kortienske kiseline metilprednizolona
primenom PAMPA testa.
Procena permeabilnosti i retencije u koži izvršena je na hidrofobnoj Millipore
PVDF PAMPA mikrotitarskoj ploči sa 96 odeljaka. Praćena je difuzija ispitivanih
jedinjenja kroz membranu koju čine 70 % silikonsko ulje i 30 % izopropilmiristat.
Koncentracije u polaznim rastvorima, donorskim i akceptorskim odeljcima određene su
primenom LC‐MS/MS metode.
Primenom PAMPA testa određeni su koeficijenti permeabilnosti (logPe) i
retencije (R). Vrednosti logPe su u opsegu od ‐6,81 do ‐5,09, dok su vrednosti R u
opsegu 1,52 ‐ 65,25. Jedinjenje sa najnižom vrednošću logPe je MPMGB, dok su za
MPEMP određene najviše vrednosti parametara logPe i R, te se od ovog derivata mogu
očekivati najveća permeabilnost i retencija u koži.
Permeabilnost i retencija u koži pet amida (MPMA, MPMAB, MPMAIB, MPMGB i
MPPA) i jednog tioestra (MPEMP) kortienske kiseline metilprednizolona procenjeni su
primenom PAMPA testa. Najviše vrednosti parametara logPe i R su dobijene za MPEMP,
te se ovaj derivat izdvaja kao najpovoljniji za primenu na kožu.
AB  - Amides or esters of methylprednisolone‐derived cortienic acid are potential soft glucocorticoids with fewer side effects in comparison to traditional glucocorticoids. Retention and permeability are important properties of soft glucocorticoids for local skin application which could significantly influence their activity and occurrence of side effects. PAMPA (Parallel Artificial Membrane Permeability Assay) is one of the mostly used in vitro methods for the estimation of these properties. The aim of this study was estimation of skin permeability and retention of five amides (MPMA, MPMAB, MPMAIB, MPMGB and MPPA) and one thioester (MPEMP) of metilprednisolone ‐ derived cortienic acid using PAMPA. Estimation of skin permeability and retention was performed on hydrophobic Millipore PVDF PAMPA microtiter 96‐well plate. Diffusion of tested compounds through membrane, consisting of 70% silicon oil and 30% isopropyl myristate, was tested. Concentrations in starting solutions, as well as in donor and acceptor compartments were determined using LC‐MS/MS method. PAMPA permeability coefficients (logPe) and retention (R) were determined. logPe values ranged from ‐6.81 to ‐5.09, whereas R values ranged from 1.52 to 65.25. Derivative with the lowest value of logPe was MPMGB, whereas the highest values of logPe and R were determined for MPEMP. Therefore, highest skin permeability and retention could be expected from MPEMP. Skin permeability and retention of five amides (MPMA, MPMAB, MPMAIB, MPMGB and MPPA) and one thioester (MPEMP) of metilprednisolone ‐ derived cortienic acid was estimated by use of PAMPA. The highest values of logPe and R were calculated for MPEMP, which could be considered the best candidate for skin application.
PB  - Savez farmaceutskih udruženja Srbije
C3  - Arhiv za farmaciju
T1  - Primena PAMPA testa u proceni permeabilnosti i retencije u koži derivata kortienske kiseline metilprednizolona kao potencijalnih soft glukokortikoida
T1  - The use of PAMPA for skin permeability and retention evaluation of metilprednisolone - derived cortienic acid derivatives as potential soft glucocorticoids
VL  - 68
IS  - 3
SP  - 387
EP  - 388
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5454
ER  - 

@conference{
author = "Bošković, Jelena and Marković, Jelena and Dobričić, Vladimir and Čudina, Olivera",
year = "2018",
abstract = "Amidi ili estri kortienske kiseline metilprednizolona predstavljaju potencijalne
soft glukokortikoide sa manje izraženim neželjenim efektima u odnosu na
konvencionalne glukokortikoide. Retencija i permeabilnost su važne osobine soft
glukokortikoida za primenu na kožu koje mogu značajno uticati na njihovu aktivnost i
pojavu neželjenih efekata. Jedna od in vitro metoda koja se najčešće koristi za procenu
ovih osobina je PAMPA (Parallel Artificial Membrane Permeability Assay). Cilj ovog
rada je procena permeabilnosti i retencije u koži pet amida (MPMA, MPMAB, MPMAIB,
MPMGB i MPPA) i jednog tioestra (MPEMP) kortienske kiseline metilprednizolona
primenom PAMPA testa.
Procena permeabilnosti i retencije u koži izvršena je na hidrofobnoj Millipore
PVDF PAMPA mikrotitarskoj ploči sa 96 odeljaka. Praćena je difuzija ispitivanih
jedinjenja kroz membranu koju čine 70 % silikonsko ulje i 30 % izopropilmiristat.
Koncentracije u polaznim rastvorima, donorskim i akceptorskim odeljcima određene su
primenom LC‐MS/MS metode.
Primenom PAMPA testa određeni su koeficijenti permeabilnosti (logPe) i
retencije (R). Vrednosti logPe su u opsegu od ‐6,81 do ‐5,09, dok su vrednosti R u
opsegu 1,52 ‐ 65,25. Jedinjenje sa najnižom vrednošću logPe je MPMGB, dok su za
MPEMP određene najviše vrednosti parametara logPe i R, te se od ovog derivata mogu
očekivati najveća permeabilnost i retencija u koži.
Permeabilnost i retencija u koži pet amida (MPMA, MPMAB, MPMAIB, MPMGB i
MPPA) i jednog tioestra (MPEMP) kortienske kiseline metilprednizolona procenjeni su
primenom PAMPA testa. Najviše vrednosti parametara logPe i R su dobijene za MPEMP,
te se ovaj derivat izdvaja kao najpovoljniji za primenu na kožu., Amides or esters of methylprednisolone‐derived cortienic acid are potential soft glucocorticoids with fewer side effects in comparison to traditional glucocorticoids. Retention and permeability are important properties of soft glucocorticoids for local skin application which could significantly influence their activity and occurrence of side effects. PAMPA (Parallel Artificial Membrane Permeability Assay) is one of the mostly used in vitro methods for the estimation of these properties. The aim of this study was estimation of skin permeability and retention of five amides (MPMA, MPMAB, MPMAIB, MPMGB and MPPA) and one thioester (MPEMP) of metilprednisolone ‐ derived cortienic acid using PAMPA. Estimation of skin permeability and retention was performed on hydrophobic Millipore PVDF PAMPA microtiter 96‐well plate. Diffusion of tested compounds through membrane, consisting of 70% silicon oil and 30% isopropyl myristate, was tested. Concentrations in starting solutions, as well as in donor and acceptor compartments were determined using LC‐MS/MS method. PAMPA permeability coefficients (logPe) and retention (R) were determined. logPe values ranged from ‐6.81 to ‐5.09, whereas R values ranged from 1.52 to 65.25. Derivative with the lowest value of logPe was MPMGB, whereas the highest values of logPe and R were determined for MPEMP. Therefore, highest skin permeability and retention could be expected from MPEMP. Skin permeability and retention of five amides (MPMA, MPMAB, MPMAIB, MPMGB and MPPA) and one thioester (MPEMP) of metilprednisolone ‐ derived cortienic acid was estimated by use of PAMPA. The highest values of logPe and R were calculated for MPEMP, which could be considered the best candidate for skin application.",
publisher = "Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Primena PAMPA testa u proceni permeabilnosti i retencije u koži derivata kortienske kiseline metilprednizolona kao potencijalnih soft glukokortikoida, The use of PAMPA for skin permeability and retention evaluation of metilprednisolone - derived cortienic acid derivatives as potential soft glucocorticoids",
volume = "68",
number = "3",
pages = "387-388",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5454"
}

Bošković, J., Marković, J., Dobričić, V.,& Čudina, O.. (2018). Primena PAMPA testa u proceni permeabilnosti i retencije u koži derivata kortienske kiseline metilprednizolona kao potencijalnih soft glukokortikoida. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije., 68(3), 387-388.
https://hdl.handle.net/21.15107/rcub_farfar_5454

Bošković J, Marković J, Dobričić V, Čudina O. Primena PAMPA testa u proceni permeabilnosti i retencije u koži derivata kortienske kiseline metilprednizolona kao potencijalnih soft glukokortikoida. in Arhiv za farmaciju. 2018;68(3):387-388.
https://hdl.handle.net/21.15107/rcub_farfar_5454 .

Bošković, Jelena, Marković, Jelena, Dobričić, Vladimir, Čudina, Olivera, "Primena PAMPA testa u proceni permeabilnosti i retencije u koži derivata kortienske kiseline metilprednizolona kao potencijalnih soft glukokortikoida" in Arhiv za farmaciju, 68, no. 3 (2018):387-388,
https://hdl.handle.net/21.15107/rcub_farfar_5454 .

TY  - JOUR
AU  - Rupar, Jelena
AU  - Dobričić, Vladimir
AU  - Aleksić, Mara
AU  - Brborić, Jasmina
AU  - Čudina, Olivera
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3033
AB  - Acridine ring can be found in molecules used in many different spheres, including industry and medicine. Nowadays, even acridines with antibacterial activity are of research interest due to increasing bacterial resistance. Some acridine derivatives showed antimalarial or antiviral activity. Acridine derivatives were also investigated for antitumor activity due to the interaction with topoisomerase II and DNA base pairs. Considering these possible uses of acridine derivatives, this work was made as overview of all significant structure characteristics for specific action of these compounds.
PB  - Univerzitet u Kragujevcu - Prirodno-matematički fakultet, Kragujevac
T2  - Kragujevac Journal of Science
T1  - A review of published data on acridine derivatives with different biological activities
IS  - 40
SP  - 83
EP  - 101
DO  - 10.5937/KgJSci1840083R
ER  - 

@article{
author = "Rupar, Jelena and Dobričić, Vladimir and Aleksić, Mara and Brborić, Jasmina and Čudina, Olivera",
year = "2018",
abstract = "Acridine ring can be found in molecules used in many different spheres, including industry and medicine. Nowadays, even acridines with antibacterial activity are of research interest due to increasing bacterial resistance. Some acridine derivatives showed antimalarial or antiviral activity. Acridine derivatives were also investigated for antitumor activity due to the interaction with topoisomerase II and DNA base pairs. Considering these possible uses of acridine derivatives, this work was made as overview of all significant structure characteristics for specific action of these compounds.",
publisher = "Univerzitet u Kragujevcu - Prirodno-matematički fakultet, Kragujevac",
journal = "Kragujevac Journal of Science",
title = "A review of published data on acridine derivatives with different biological activities",
number = "40",
pages = "83-101",
doi = "10.5937/KgJSci1840083R"
}

Rupar, J., Dobričić, V., Aleksić, M., Brborić, J.,& Čudina, O.. (2018). A review of published data on acridine derivatives with different biological activities. in Kragujevac Journal of Science
Univerzitet u Kragujevcu - Prirodno-matematički fakultet, Kragujevac.(40), 83-101.
https://doi.org/10.5937/KgJSci1840083R

Rupar J, Dobričić V, Aleksić M, Brborić J, Čudina O. A review of published data on acridine derivatives with different biological activities. in Kragujevac Journal of Science. 2018;(40):83-101.
doi:10.5937/KgJSci1840083R .

Rupar, Jelena, Dobričić, Vladimir, Aleksić, Mara, Brborić, Jasmina, Čudina, Olivera, "A review of published data on acridine derivatives with different biological activities" in Kragujevac Journal of Science, no. 40 (2018):83-101,
https://doi.org/10.5937/KgJSci1840083R . .

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Stanišić, Aleksa
AU  - Vladimirov, Sote
AU  - Čudina, Olivera
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3209
AB  - Octanol-water partition coefficients (log Po/w) of fifteen previously synthesized 17 beta-carboxamide glucocorticoid derivatives and prednisolone were determined using shake-flask method. The retention behavior of selected compounds was tested in five reversed-phased thin-layer chromatography (RP-TLC) systems, consisting of water and organic solvent (acetonitrile, acetone, ethanol 96%, methanol, or tetrahydrofuran), and chromatography parameters (R-M(0), S, and C-0) were calculated. Simple linear regression (SLR) analysis was performed, and the correlation between log Po/w and chromatography parameters was tested. The most appropriate RP-TLC system for log Po/w prediction was that consisting of water and ethanol 96% as the mobile phase. Statisitical evaluation of the quality of models created using this system proved their reliability for log Po/w prediction of new 17 beta-carboxamide glucocorticoid derivatives, and the model with the most favorable statistical parameters was underlined.
PB  - Akademiai Kiado Zrt, Budapest
T2  - Journal of Planar Chromatography - Modern TLC
T1  - Development of a Reversed-Phased Thin-Layer
Chromatography Method for the Lipophilicity Prediction of
17β-Carboxamide Glucocorticoid Derivatives
VL  - 31
IS  - 3
SP  - 250
EP  - 256
DO  - 10.1556/1006.2018.31.3.11
ER  - 

@article{
author = "Dobričić, Vladimir and Stanišić, Aleksa and Vladimirov, Sote and Čudina, Olivera",
year = "2018",
abstract = "Octanol-water partition coefficients (log Po/w) of fifteen previously synthesized 17 beta-carboxamide glucocorticoid derivatives and prednisolone were determined using shake-flask method. The retention behavior of selected compounds was tested in five reversed-phased thin-layer chromatography (RP-TLC) systems, consisting of water and organic solvent (acetonitrile, acetone, ethanol 96%, methanol, or tetrahydrofuran), and chromatography parameters (R-M(0), S, and C-0) were calculated. Simple linear regression (SLR) analysis was performed, and the correlation between log Po/w and chromatography parameters was tested. The most appropriate RP-TLC system for log Po/w prediction was that consisting of water and ethanol 96% as the mobile phase. Statisitical evaluation of the quality of models created using this system proved their reliability for log Po/w prediction of new 17 beta-carboxamide glucocorticoid derivatives, and the model with the most favorable statistical parameters was underlined.",
publisher = "Akademiai Kiado Zrt, Budapest",
journal = "Journal of Planar Chromatography - Modern TLC",
title = "Development of a Reversed-Phased Thin-Layer
Chromatography Method for the Lipophilicity Prediction of
17β-Carboxamide Glucocorticoid Derivatives",
volume = "31",
number = "3",
pages = "250-256",
doi = "10.1556/1006.2018.31.3.11"
}

Dobričić, V., Stanišić, A., Vladimirov, S.,& Čudina, O.. (2018). Development of a Reversed-Phased Thin-Layer
Chromatography Method for the Lipophilicity Prediction of
17β-Carboxamide Glucocorticoid Derivatives. in Journal of Planar Chromatography - Modern TLC
Akademiai Kiado Zrt, Budapest., 31(3), 250-256.
https://doi.org/10.1556/1006.2018.31.3.11

Dobričić V, Stanišić A, Vladimirov S, Čudina O. Development of a Reversed-Phased Thin-Layer
Chromatography Method for the Lipophilicity Prediction of
17β-Carboxamide Glucocorticoid Derivatives. in Journal of Planar Chromatography - Modern TLC. 2018;31(3):250-256.
doi:10.1556/1006.2018.31.3.11 .

Dobričić, Vladimir, Stanišić, Aleksa, Vladimirov, Sote, Čudina, Olivera, "Development of a Reversed-Phased Thin-Layer
Chromatography Method for the Lipophilicity Prediction of
17β-Carboxamide Glucocorticoid Derivatives" in Journal of Planar Chromatography - Modern TLC, 31, no. 3 (2018):250-256,
https://doi.org/10.1556/1006.2018.31.3.11 . .

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Drvenica, Ivana
AU  - Stancić, Ana
AU  - Mihailović, Marija
AU  - Čudina, Olivera
AU  - Bugarski, Diana
AU  - Ilić, Vesna
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3162
AB  - The biological activity of three previously synthesized 17 beta-carboxamide glucocorticoids (BG, BEG, and MPEA) was tested in vitro on mitogen stimulated and non-stimulated peripheral blood mononuclear cells (MNCs) and granulocytes from human healthy donors, and the results were compared to the conventional glucocorticoid dexamethasone. The tested 17 beta-carboxamide glucocorticoids did not induce decreases in MNC viability and proliferation, while modulation of reactive oxygen species (ROS) synthesis in granulocytes was dependent on the cell donor. The obtained results indicate the possibility of avoidance of strong lymphocyte suppression, which is generally recognized during administration of conventional glucocorticoids. Furthermore, the metabolism of the tested derivatives was predicted in silico. The predicted metabolites were synthesized and the in silico results were confirmed by in vitro evaluation of the metabolism of BG, BEG, and MPEA in human serum and in cultures of peripheral blood MNCs. The results of the biological activity and metabolism evaluation and of previous in vivo evaluations of biological activity indicate the soft drug nature of BG, BEG, and MPEA. In order to be fully considered as soft glucocorticoids, further investigations on the toxicity and activity of the formed metabolites are required.
PB  - Wiley-VCH Verlag GMBH, Weinheim
T2  - Archiv der Pharmazie
T1  - Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes
VL  - 351
IS  - 5
DO  - 10.1002/ardp.201700371
ER  - 

@article{
author = "Dobričić, Vladimir and Drvenica, Ivana and Stancić, Ana and Mihailović, Marija and Čudina, Olivera and Bugarski, Diana and Ilić, Vesna",
year = "2018",
abstract = "The biological activity of three previously synthesized 17 beta-carboxamide glucocorticoids (BG, BEG, and MPEA) was tested in vitro on mitogen stimulated and non-stimulated peripheral blood mononuclear cells (MNCs) and granulocytes from human healthy donors, and the results were compared to the conventional glucocorticoid dexamethasone. The tested 17 beta-carboxamide glucocorticoids did not induce decreases in MNC viability and proliferation, while modulation of reactive oxygen species (ROS) synthesis in granulocytes was dependent on the cell donor. The obtained results indicate the possibility of avoidance of strong lymphocyte suppression, which is generally recognized during administration of conventional glucocorticoids. Furthermore, the metabolism of the tested derivatives was predicted in silico. The predicted metabolites were synthesized and the in silico results were confirmed by in vitro evaluation of the metabolism of BG, BEG, and MPEA in human serum and in cultures of peripheral blood MNCs. The results of the biological activity and metabolism evaluation and of previous in vivo evaluations of biological activity indicate the soft drug nature of BG, BEG, and MPEA. In order to be fully considered as soft glucocorticoids, further investigations on the toxicity and activity of the formed metabolites are required.",
publisher = "Wiley-VCH Verlag GMBH, Weinheim",
journal = "Archiv der Pharmazie",
title = "Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes",
volume = "351",
number = "5",
doi = "10.1002/ardp.201700371"
}

Dobričić, V., Drvenica, I., Stancić, A., Mihailović, M., Čudina, O., Bugarski, D.,& Ilić, V.. (2018). Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes. in Archiv der Pharmazie
Wiley-VCH Verlag GMBH, Weinheim., 351(5).
https://doi.org/10.1002/ardp.201700371

Dobričić V, Drvenica I, Stancić A, Mihailović M, Čudina O, Bugarski D, Ilić V. Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes. in Archiv der Pharmazie. 2018;351(5).
doi:10.1002/ardp.201700371 .

Dobričić, Vladimir, Drvenica, Ivana, Stancić, Ana, Mihailović, Marija, Čudina, Olivera, Bugarski, Diana, Ilić, Vesna, "Investigation of metabolic properties and effects of 17 beta-carboxamide glucocorticoids on human peripheral blood leukocytes" in Archiv der Pharmazie, 351, no. 5 (2018),
https://doi.org/10.1002/ardp.201700371 . .

TY  - JOUR
AU  - Damnjanović, Danijela
AU  - Dobričić, Vladimir
AU  - Čudina, Olivera
AU  - Vladimirov, Sote
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3101
AB  - Acetylsalicylic acid belongs to nonsteroidal anti-inflammatory drugs with antiinflammatory, analgesic and antipyretic properties. The aim of this work was development and validation of HPLC method for qualitative and quantitative analysis of acetylsalicylic acid and its major degradation product, salicylic acid, in dosage forms. The optimal separation was achived using Zorbax Eclipse XDB-C18 Analytical column (4,6x150 mm, particle size 5 μm) thermostated at 35°C. Mobile phase consisted of eluents A and B in ratio 65:35 (V/V). As the eluent A, water of HPLC purity and 85% phosphoric acid in ratio 80:0.5 (V/V) were used, while acetonitrile was used as the eluent B. The flow rate was 1.0 mL/min and UV detection was performed at 240 nm. The method was validated in terms of selectivity, linearity, precision, accuracy and robustness for both analytes, as well as limits of detection and quantification for salicylic acid. The obtained results meet the requirements of analytical procedures validation. The proposed HPLC method was applied in qualitative and quantitative analysis of acetylsalicylic and salicylic acids in six different forms of drugs. All obtained results meet the requirements of manufacturer specifications. The established HPLC method was found to be rapid, simple, accurate and selective for simultaneous determination of acetylsalicylic and salicylic acids in dosage forms.
AB  - Acetilsalicilna kiselina pripada grupi nesteroidnih antiinflamatornih lekova koji ispoljavaju antiinflamatorno, analgetičko i antipiretičko delovanje. Cilj ovog rada je bio razvoj i validacija HPLC metode za kvalitativnu i kvantitativnu analizu acetilsalicilne kiseline i njenog degradacionog proizvoda, salicilne kiseline, u doziranim oblicima. Optimalno razdvajanje ispitivanih analita postignuto je na koloni Zorbax Eclipse XDB-C18 Analytical (4,6x150 mm, veličina čestica 5 μm) na temperaturi od 35°C. Mobilnu fazu čine smeša A i B u odnosu 65:35 (V/V). Smeša A je voda HPLC čistoće i 85% fosforna kiselina u odnosu 80:0,5 (V/V), a B je acetonitril. Protok je bio 1,0 mL/min, a talasna dužina detekcije 240 nm. Metoda je validirana i ispitani su sledeći parametri validacije: selektivnost, linearnost, preciznost, tačnost i robusnost za oba analita, kao i limiti detekcije i kvantifikacije za salicilnu kiselinu. Dobijene vrednosti su u skladu sa definisanim kriterijumima za validaciju metode. Predložena HPLC metoda je primenjena za kvalitativnu i kvantitativnu analizu acetilsalicilne i salicilne kiseline u šest različitih komercijalnih preparata. Svi rezultati ispitivanja su u dozvoljenim granicama specifikacija proizvođača. Predložena HPLC metoda pod datim eksperimentalnim uslovima predstavlja brz, jednostavan, tačan i selektivan postupak za istovremeno određivanje acetilsalicilne i salicilne kiseline u doziranim oblicima.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Development and validation of liquid chromatography method for determination of acetylsalicylic and salicylic acid in dosage forms
T1  - Razvoj i validacija metode tečne hromatografije za određivanje acetilsalicilne i salicilne kiseline u doziranim oblicima
VL  - 68
IS  - 4
SP  - 885
EP  - 899
DO  - 10.5937/ArhFarm1804885D
ER  - 

@article{
author = "Damnjanović, Danijela and Dobričić, Vladimir and Čudina, Olivera and Vladimirov, Sote",
year = "2018",
abstract = "Acetylsalicylic acid belongs to nonsteroidal anti-inflammatory drugs with antiinflammatory, analgesic and antipyretic properties. The aim of this work was development and validation of HPLC method for qualitative and quantitative analysis of acetylsalicylic acid and its major degradation product, salicylic acid, in dosage forms. The optimal separation was achived using Zorbax Eclipse XDB-C18 Analytical column (4,6x150 mm, particle size 5 μm) thermostated at 35°C. Mobile phase consisted of eluents A and B in ratio 65:35 (V/V). As the eluent A, water of HPLC purity and 85% phosphoric acid in ratio 80:0.5 (V/V) were used, while acetonitrile was used as the eluent B. The flow rate was 1.0 mL/min and UV detection was performed at 240 nm. The method was validated in terms of selectivity, linearity, precision, accuracy and robustness for both analytes, as well as limits of detection and quantification for salicylic acid. The obtained results meet the requirements of analytical procedures validation. The proposed HPLC method was applied in qualitative and quantitative analysis of acetylsalicylic and salicylic acids in six different forms of drugs. All obtained results meet the requirements of manufacturer specifications. The established HPLC method was found to be rapid, simple, accurate and selective for simultaneous determination of acetylsalicylic and salicylic acids in dosage forms., Acetilsalicilna kiselina pripada grupi nesteroidnih antiinflamatornih lekova koji ispoljavaju antiinflamatorno, analgetičko i antipiretičko delovanje. Cilj ovog rada je bio razvoj i validacija HPLC metode za kvalitativnu i kvantitativnu analizu acetilsalicilne kiseline i njenog degradacionog proizvoda, salicilne kiseline, u doziranim oblicima. Optimalno razdvajanje ispitivanih analita postignuto je na koloni Zorbax Eclipse XDB-C18 Analytical (4,6x150 mm, veličina čestica 5 μm) na temperaturi od 35°C. Mobilnu fazu čine smeša A i B u odnosu 65:35 (V/V). Smeša A je voda HPLC čistoće i 85% fosforna kiselina u odnosu 80:0,5 (V/V), a B je acetonitril. Protok je bio 1,0 mL/min, a talasna dužina detekcije 240 nm. Metoda je validirana i ispitani su sledeći parametri validacije: selektivnost, linearnost, preciznost, tačnost i robusnost za oba analita, kao i limiti detekcije i kvantifikacije za salicilnu kiselinu. Dobijene vrednosti su u skladu sa definisanim kriterijumima za validaciju metode. Predložena HPLC metoda je primenjena za kvalitativnu i kvantitativnu analizu acetilsalicilne i salicilne kiseline u šest različitih komercijalnih preparata. Svi rezultati ispitivanja su u dozvoljenim granicama specifikacija proizvođača. Predložena HPLC metoda pod datim eksperimentalnim uslovima predstavlja brz, jednostavan, tačan i selektivan postupak za istovremeno određivanje acetilsalicilne i salicilne kiseline u doziranim oblicima.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Development and validation of liquid chromatography method for determination of acetylsalicylic and salicylic acid in dosage forms, Razvoj i validacija metode tečne hromatografije za određivanje acetilsalicilne i salicilne kiseline u doziranim oblicima",
volume = "68",
number = "4",
pages = "885-899",
doi = "10.5937/ArhFarm1804885D"
}

Damnjanović, D., Dobričić, V., Čudina, O.,& Vladimirov, S.. (2018). Development and validation of liquid chromatography method for determination of acetylsalicylic and salicylic acid in dosage forms. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 68(4), 885-899.
https://doi.org/10.5937/ArhFarm1804885D

Damnjanović D, Dobričić V, Čudina O, Vladimirov S. Development and validation of liquid chromatography method for determination of acetylsalicylic and salicylic acid in dosage forms. in Arhiv za farmaciju. 2018;68(4):885-899.
doi:10.5937/ArhFarm1804885D .

Damnjanović, Danijela, Dobričić, Vladimir, Čudina, Olivera, Vladimirov, Sote, "Development and validation of liquid chromatography method for determination of acetylsalicylic and salicylic acid in dosage forms" in Arhiv za farmaciju, 68, no. 4 (2018):885-899,
https://doi.org/10.5937/ArhFarm1804885D . .