TY  - JOUR
AU  - Nedeljković, Nikola
AU  - Nikolić, Miloš
AU  - Čanović, Petar
AU  - Zarić, Milan
AU  - Živković-Zarić, Radica
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Nikolić, Marina
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Dobričić, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5449
AB  - The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8–14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1–7 and 8–14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 μM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.
PB  - MDPI
T2  - Pharmaceutics
T1  - Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen
VL  - 16
IS  - 1
SP  - 1
DO  - 10.3390/pharmaceutics16010001
ER  - 

@article{
author = "Nedeljković, Nikola and Nikolić, Miloš and Čanović, Petar and Zarić, Milan and Živković-Zarić, Radica and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Nikolić, Marina and Jakovljević, Vladimir and Vujić, Zorica and Dobričić, Vladimir",
year = "2024",
abstract = "The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8–14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1–7 and 8–14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 μM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen",
volume = "16",
number = "1",
pages = "1",
doi = "10.3390/pharmaceutics16010001"
}

Nedeljković, N., Nikolić, M., Čanović, P., Zarić, M., Živković-Zarić, R., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Nikolić, M., Jakovljević, V., Vujić, Z.,& Dobričić, V.. (2024). Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen. in Pharmaceutics
MDPI., 16(1), 1.
https://doi.org/10.3390/pharmaceutics16010001

Nedeljković N, Nikolić M, Čanović P, Zarić M, Živković-Zarić R, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Nikolić M, Jakovljević V, Vujić Z, Dobričić V. Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen. in Pharmaceutics. 2024;16(1):1.
doi:10.3390/pharmaceutics16010001 .

Nedeljković, Nikola, Nikolić, Miloš, Čanović, Petar, Zarić, Milan, Živković-Zarić, Radica, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Nikolić, Marina, Jakovljević, Vladimir, Vujić, Zorica, Dobričić, Vladimir, "Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen" in Pharmaceutics, 16, no. 1 (2024):1,
https://doi.org/10.3390/pharmaceutics16010001 . .

TY  - JOUR
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Jeremić, Nevena
AU  - Novaković, Jovana
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4756
AB  - The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1–5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 μM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agent
PB  - MDPI
T2  - Pharmaceuticals
T1  - Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen
VL  - 16
IS  - 5
DO  - 10.3390/ph16050666
ER  - 

@article{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Jeremić, Nevena and Novaković, Jovana and Jakovljević, Vladimir and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1–5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 μM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agent",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen",
volume = "16",
number = "5",
doi = "10.3390/ph16050666"
}

Nedeljković, N., Dobričić, V., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Jeremić, N., Novaković, J., Jakovljević, V., Vujić, Z.,& Nikolić, M.. (2023). Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen. in Pharmaceuticals
MDPI., 16(5).
https://doi.org/10.3390/ph16050666

Nedeljković N, Dobričić V, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Jeremić N, Novaković J, Jakovljević V, Vujić Z, Nikolić M. Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen. in Pharmaceuticals. 2023;16(5).
doi:10.3390/ph16050666 .

Nedeljković, Nikola, Dobričić, Vladimir, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Jeremić, Nevena, Novaković, Jovana, Jakovljević, Vladimir, Vujić, Zorica, Nikolić, Miloš, "Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen" in Pharmaceuticals, 16, no. 5 (2023),
https://doi.org/10.3390/ph16050666 . .

TY  - JOUR
AU  - Coskun, Goknil Pelin
AU  - Ozhan, Yagmur
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Reis, Rengin
AU  - Sipahi, Hande
AU  - Sahin, Zafer
AU  - Demirayak, Seref
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4764
AB  - Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds 7a, 7d, and 7f were promising. Among these, 7f (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds 7a, 7d and 7f were also tested for their cytotoxic effects on healthy cell line but only compound 7d showed selectivity. Compounds 7a, 7d, and 7f showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC50 value was observed for 7c (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds 7a (3.78 µM), 7c (2.60 µM), 7e (3.3 µM), and 7f (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds 7c, 7e, and 7f to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, 7a and 7f were identified as the most promising compounds.
PB  - MDPI
T2  - Pharmaceutics
T1  - Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer
VL  - 15
IS  - 5
DO  - https://doi.org/10.3390/pharmaceutics15051441
ER  - 

@article{
author = "Coskun, Goknil Pelin and Ozhan, Yagmur and Dobričić, Vladimir and Bošković, Jelena and Reis, Rengin and Sipahi, Hande and Sahin, Zafer and Demirayak, Seref",
year = "2023",
abstract = "Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds 7a, 7d, and 7f were promising. Among these, 7f (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds 7a, 7d and 7f were also tested for their cytotoxic effects on healthy cell line but only compound 7d showed selectivity. Compounds 7a, 7d, and 7f showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC50 value was observed for 7c (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds 7a (3.78 µM), 7c (2.60 µM), 7e (3.3 µM), and 7f (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds 7c, 7e, and 7f to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, 7a and 7f were identified as the most promising compounds.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer",
volume = "15",
number = "5",
doi = "https://doi.org/10.3390/pharmaceutics15051441"
}

Coskun, G. P., Ozhan, Y., Dobričić, V., Bošković, J., Reis, R., Sipahi, H., Sahin, Z.,& Demirayak, S.. (2023). Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer. in Pharmaceutics
MDPI., 15(5).
https://doi.org/https://doi.org/10.3390/pharmaceutics15051441

Coskun GP, Ozhan Y, Dobričić V, Bošković J, Reis R, Sipahi H, Sahin Z, Demirayak S. Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer. in Pharmaceutics. 2023;15(5).
doi:https://doi.org/10.3390/pharmaceutics15051441 .

Coskun, Goknil Pelin, Ozhan, Yagmur, Dobričić, Vladimir, Bošković, Jelena, Reis, Rengin, Sipahi, Hande, Sahin, Zafer, Demirayak, Seref, "Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer" in Pharmaceutics, 15, no. 5 (2023),
https://doi.org/https://doi.org/10.3390/pharmaceutics15051441 . .

TY  - CONF
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Jeremić, Nevena
AU  - Novaković, Jovana
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5476
AB  - The aim of the conducted study was to develop new potential dual COX-2 and 5-LOX
inhibitors based on naproxen scaffold. We performed the evaluation of in vivo and in vitro
anti-inflammatory activity of newly synthesized thiourea derivatives of naproxen containing
m-anisidine and N-methyl tryptophan methyl ester in a side chain. An in vivo study
was carried out using a carrageenan-induced paw edema model of acute inflammation.
COX-2 and 5-LOX inhibitory potential of synthesized compounds was evaluated using
fluorometric inhibitor screening kits. In silico study was performed in OEDocking 3.2.0.2
software with the FRED tool. Two investigated derivatives exhibited comparable anti-inflammatory
activity to naproxen (56.32%) four hours after injection of carrageenan, with
the percentage of inhibition being 54.01% (m-anisidine derivative) and 54.12% (N-methyl
tryptophan methyl ester derivative). In vitro studies of COX-2 inhibition demonstrated that
none of the tested compounds achieved 50% inhibition at concentrations below 100 μM,
whereas the m-anisidine derivative accomplished comparable inhibition of 5-LOX (IC50 =
0.30 μM) to commercial 5-LOX inhibitor zileuton (IC50 = 0.36 μM). Inability of the tested
compounds to form three hydrogen bonds with ARG120 and TYR355 could be a reason
why these compounds showed weak COX-2 inhibition. The m-anisidine derivative formed
a more stable complex with the 5-LOX enzyme (−8.39 kcal/mol), compared to N-methyl
tryptophan methyl ester derivative (−7.98 kcal/mol), with the absence of the iron ion chelation
in the active site in both cases. The significant in vivo anti-inflammatory activity of
the m-anisidine derivative, together with the potent inhibition of 5-LOX, highlighted this
compound as a promising anti-inflammatory agent.
PB  - Fakultet medicinskih nauka Univerziteta u Kragujevcu
C3  - 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia
T1  - Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5476
ER  - 

@conference{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Jeremić, Nevena and Novaković, Jovana and Jakovljević, Vladimir and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "The aim of the conducted study was to develop new potential dual COX-2 and 5-LOX
inhibitors based on naproxen scaffold. We performed the evaluation of in vivo and in vitro
anti-inflammatory activity of newly synthesized thiourea derivatives of naproxen containing
m-anisidine and N-methyl tryptophan methyl ester in a side chain. An in vivo study
was carried out using a carrageenan-induced paw edema model of acute inflammation.
COX-2 and 5-LOX inhibitory potential of synthesized compounds was evaluated using
fluorometric inhibitor screening kits. In silico study was performed in OEDocking 3.2.0.2
software with the FRED tool. Two investigated derivatives exhibited comparable anti-inflammatory
activity to naproxen (56.32%) four hours after injection of carrageenan, with
the percentage of inhibition being 54.01% (m-anisidine derivative) and 54.12% (N-methyl
tryptophan methyl ester derivative). In vitro studies of COX-2 inhibition demonstrated that
none of the tested compounds achieved 50% inhibition at concentrations below 100 μM,
whereas the m-anisidine derivative accomplished comparable inhibition of 5-LOX (IC50 =
0.30 μM) to commercial 5-LOX inhibitor zileuton (IC50 = 0.36 μM). Inability of the tested
compounds to form three hydrogen bonds with ARG120 and TYR355 could be a reason
why these compounds showed weak COX-2 inhibition. The m-anisidine derivative formed
a more stable complex with the 5-LOX enzyme (−8.39 kcal/mol), compared to N-methyl
tryptophan methyl ester derivative (−7.98 kcal/mol), with the absence of the iron ion chelation
in the active site in both cases. The significant in vivo anti-inflammatory activity of
the m-anisidine derivative, together with the potent inhibition of 5-LOX, highlighted this
compound as a promising anti-inflammatory agent.",
publisher = "Fakultet medicinskih nauka Univerziteta u Kragujevcu",
journal = "9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia",
title = "Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5476"
}

Nedeljković, N., Dobričić, V., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Jeremić, N., Novaković, J., Jakovljević, V., Vujić, Z.,& Nikolić, M.. (2023). Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach. in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia
Fakultet medicinskih nauka Univerziteta u Kragujevcu..
https://hdl.handle.net/21.15107/rcub_farfar_5476

Nedeljković N, Dobričić V, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Jeremić N, Novaković J, Jakovljević V, Vujić Z, Nikolić M. Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach. in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_5476 .

Nedeljković, Nikola, Dobričić, Vladimir, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Jeremić, Nevena, Novaković, Jovana, Jakovljević, Vladimir, Vujić, Zorica, Nikolić, Miloš, "Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach" in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5476 .

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  - 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  - 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  - 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  - 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 .