TY  - JOUR
AU  - Obradović, Darija
AU  - Savić, Jelena
AU  - Joksimović, Jovana
AU  - Marković, Bojan
AU  - Vujić, Zorica
AU  - Lazović, Saša
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5549
AB  - Abstract: The retention profile of six serotonin receptor ligands such as arylpiperazines (aripiprazole, ziprasidone, risperidone), and benzothiazepine derivatives (olanzapine, mianserin, quetiapine), was investigated on C8 alkyl and pentafluorophenylpropyl stationary phases. The experimental design methodology was used to define their retention behavior and achieve acceptable separation results. Both phases showed satisfactory selectivity for all compounds. The optimal separation among the structurally related arylpiperazines and benzothiazepines was found with the C8 phase at 25°C, using acetonitrile (40%, v/v) and 20 mM ammonium acetate as a mobile phase modifier. The selectivity and sensitivity performances of the selected C8 system were discussed considering the separation of aripiprazole and its related compounds. In addition, the specified conditions were validated for determining aripiprazole in pharmaceutical dosage forms. The developed reversed-phase high-performance liquid chromatography method can be successfully used for the rapid chromatographic profiling of serotonin receptor ligands and related analogs, providing increased selectivity during pharmaceutical analysis.
PB  - Springer
T2  - Journal of Analytical Chemistry
T1  - Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds
VL  - 79
IS  - 1
SP  - 95
EP  - 104
DO  - 10.1134/S1061934824010076
ER  - 

@article{
author = "Obradović, Darija and Savić, Jelena and Joksimović, Jovana and Marković, Bojan and Vujić, Zorica and Lazović, Saša",
year = "2024",
abstract = "Abstract: The retention profile of six serotonin receptor ligands such as arylpiperazines (aripiprazole, ziprasidone, risperidone), and benzothiazepine derivatives (olanzapine, mianserin, quetiapine), was investigated on C8 alkyl and pentafluorophenylpropyl stationary phases. The experimental design methodology was used to define their retention behavior and achieve acceptable separation results. Both phases showed satisfactory selectivity for all compounds. The optimal separation among the structurally related arylpiperazines and benzothiazepines was found with the C8 phase at 25°C, using acetonitrile (40%, v/v) and 20 mM ammonium acetate as a mobile phase modifier. The selectivity and sensitivity performances of the selected C8 system were discussed considering the separation of aripiprazole and its related compounds. In addition, the specified conditions were validated for determining aripiprazole in pharmaceutical dosage forms. The developed reversed-phase high-performance liquid chromatography method can be successfully used for the rapid chromatographic profiling of serotonin receptor ligands and related analogs, providing increased selectivity during pharmaceutical analysis.",
publisher = "Springer",
journal = "Journal of Analytical Chemistry",
title = "Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds",
volume = "79",
number = "1",
pages = "95-104",
doi = "10.1134/S1061934824010076"
}

Obradović, D., Savić, J., Joksimović, J., Marković, B., Vujić, Z.,& Lazović, S.. (2024). Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds. in Journal of Analytical Chemistry
Springer., 79(1), 95-104.
https://doi.org/10.1134/S1061934824010076

Obradović D, Savić J, Joksimović J, Marković B, Vujić Z, Lazović S. Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds. in Journal of Analytical Chemistry. 2024;79(1):95-104.
doi:10.1134/S1061934824010076 .

Obradović, Darija, Savić, Jelena, Joksimović, Jovana, Marković, Bojan, Vujić, Zorica, Lazović, Saša, "Rapid Reversed-Phase High-Performance Liquid Chromatography Profiling of Serotonin Receptor Ligands and their Related Compounds" in Journal of Analytical Chemistry, 79, no. 1 (2024):95-104,
https://doi.org/10.1134/S1061934824010076 . .

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  - JOUR
AU  - Savić, Jelena
AU  - Vitnik, Vesna
AU  - Obradović, Darija
AU  - Vitnik, Željko
AU  - Petrić, Vanja
AU  - Čkalovski, Teodora
AU  - Lazović, Saša
AU  - Crevar, Milkica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5444
AB  - The retention behavior of 10 previously synthesized α,β-unsaturated acids that exhibited antimicrobial activity was studied using 12 reversed-phase thin-layer chromatography (RP-TLC) systems. The mobile phases consisted of three solvent combinations (methanol‒water, acetonitrile‒water, and acetone‒water) in four different ratios (50:50, 60:40, 70:30, and 80:20, V/V). The chromatographic parameters RM0 , a, and C0 were calculated for each system. The lipophilicity parameters of the tested compounds were predicted using various computational methods. The acetone‒water system demonstrated the highest correlation coefficients between the chromatographic and calculated lipophilicity parameters, which makes it the most suitable for evaluating the lipophilicity of the tested compounds. This system successfully reflected the effect of the lipophilic properties of the compounds on their retention behavior. To elucidate the retention mechanisms, the molecular properties of the tested compounds were calculated and a genetic algorithm was used to identify the properties with the greatest influence on the retention behavior. The interpretation of these descriptors revealed structural and physicochemical properties crucial for the behavior of the tested compounds. In addition, the pharmacokinetic properties of the compounds were estimated using in silico methods. The observed correlation between the retention mechanism and physicochemical properties affecting membrane transport and physiological binding ability highlights the applicability of RP-TLC conditions for rapid profiling of newly synthesized α,β-unsaturated acids.
PB  - Springer
T2  - Journal of Planar Chromatography - Modern TLC
T1  - Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids
VL  - 36
IS  - 5
SP  - 415
EP  - 423
DO  - 10.1007/s00764-023-00274-9
ER  - 

@article{
author = "Savić, Jelena and Vitnik, Vesna and Obradović, Darija and Vitnik, Željko and Petrić, Vanja and Čkalovski, Teodora and Lazović, Saša and Crevar, Milkica",
year = "2023",
abstract = "The retention behavior of 10 previously synthesized α,β-unsaturated acids that exhibited antimicrobial activity was studied using 12 reversed-phase thin-layer chromatography (RP-TLC) systems. The mobile phases consisted of three solvent combinations (methanol‒water, acetonitrile‒water, and acetone‒water) in four different ratios (50:50, 60:40, 70:30, and 80:20, V/V). The chromatographic parameters RM0 , a, and C0 were calculated for each system. The lipophilicity parameters of the tested compounds were predicted using various computational methods. The acetone‒water system demonstrated the highest correlation coefficients between the chromatographic and calculated lipophilicity parameters, which makes it the most suitable for evaluating the lipophilicity of the tested compounds. This system successfully reflected the effect of the lipophilic properties of the compounds on their retention behavior. To elucidate the retention mechanisms, the molecular properties of the tested compounds were calculated and a genetic algorithm was used to identify the properties with the greatest influence on the retention behavior. The interpretation of these descriptors revealed structural and physicochemical properties crucial for the behavior of the tested compounds. In addition, the pharmacokinetic properties of the compounds were estimated using in silico methods. The observed correlation between the retention mechanism and physicochemical properties affecting membrane transport and physiological binding ability highlights the applicability of RP-TLC conditions for rapid profiling of newly synthesized α,β-unsaturated acids.",
publisher = "Springer",
journal = "Journal of Planar Chromatography - Modern TLC",
title = "Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids",
volume = "36",
number = "5",
pages = "415-423",
doi = "10.1007/s00764-023-00274-9"
}

Savić, J., Vitnik, V., Obradović, D., Vitnik, Ž., Petrić, V., Čkalovski, T., Lazović, S.,& Crevar, M.. (2023). Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids. in Journal of Planar Chromatography - Modern TLC
Springer., 36(5), 415-423.
https://doi.org/10.1007/s00764-023-00274-9

Savić J, Vitnik V, Obradović D, Vitnik Ž, Petrić V, Čkalovski T, Lazović S, Crevar M. Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids. in Journal of Planar Chromatography - Modern TLC. 2023;36(5):415-423.
doi:10.1007/s00764-023-00274-9 .

Savić, Jelena, Vitnik, Vesna, Obradović, Darija, Vitnik, Željko, Petrić, Vanja, Čkalovski, Teodora, Lazović, Saša, Crevar, Milkica, "Reversed-phase thin-layer chromatographic and computational evaluation of lipophilicity parameters of α,β-unsaturated acids" in Journal of Planar Chromatography - Modern TLC, 36, no. 5 (2023):415-423,
https://doi.org/10.1007/s00764-023-00274-9 . .

TY  - JOUR
AU  - Savić, Jelena
AU  - Antonijević, Marija
AU  - Crevar, Milkica
AU  - Brborić, Jasmina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4978
AB  - Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and
diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors
target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer,
atherosclerosis, Alzheimer's disease, and Parkinson`s disease. Potential cardiovascular and
hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of
selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based
on the structure of previously investigated newly synthesized β-hydroxy-β-arylpropanoic acids,
two groups of compounds were designed: analogs in which one of the benzene rings was replaced
by a pyrazole, while the carboxyl group was retained, and amides of β-hydroxy-β-arylpropanoic
acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the
enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were
compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding
energies than the designed acids, which makes them attractive target compounds for synthesis
and further examination.
AB  - Neselektivni nesteroidni antiinflamatorni lekovi poput aspirina, ibuprofena i diklofenaka
inhibiraju enzime ciklooksigenazu-1 i ciklooksigenazu-2, a selektivni inhibitori ciljaju
ciklooksigenazu-2 koja je prekomerno izražena u inflamaciji, ali takođe i kod kancera,
ateroskleroze, Parkinsonove i Alchajmerove bolesti. Potencijalni kardiovaskularni i hepatički
neželjeni efekti selektivnih inhibitora ciklooksigenaze-2 su ograničili njihovu primenu. Razvoj
selektivnih i bezbednih inhibitora ciklooksigenaze-2 ostaje veoma prioritetna oblast u otkrivanju
lekova. Na osnovu strukture prethodno istraživanih novosintetisanih β-hidroksi-β-arilpropanskih
kiselina dizajnirane su dve grupe jedinjenja: analozi u kojima je jedan od benzenovih prstenova
zamenjen pirazolom, uz zadržavanje karboksilne grupe, i amidi β-hidroksi-β-arilpropanskih
kiselina sa pirazolom. Program AutoDock Vina 1.2.0 je korišćen za dokovanje dizajniranih
jedinjenja u 3D strukturu katalitičkog mesta enzima ciklooksigenaze-2, a ostvarene interakcije su
upoređene sa interakcijama koje ostvaruje selektivni inhibitor celekoksib. Amidi su imali nižu
energiju vezivanja od kiselina, što ih čini dobrim kandidatima za sintezu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site
T1  - Doking studije nekih jedinjenja sa pirazolom u aktivnom mestu ciklooksigenaze-2
VL  - 73
IS  - 3
SP  - 205
EP  - 215
DO  - 10.5937/arhfarm73-44720
ER  - 

@article{
author = "Savić, Jelena and Antonijević, Marija and Crevar, Milkica and Brborić, Jasmina",
year = "2023",
abstract = "Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and
diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors
target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer,
atherosclerosis, Alzheimer's disease, and Parkinson`s disease. Potential cardiovascular and
hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of
selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based
on the structure of previously investigated newly synthesized β-hydroxy-β-arylpropanoic acids,
two groups of compounds were designed: analogs in which one of the benzene rings was replaced
by a pyrazole, while the carboxyl group was retained, and amides of β-hydroxy-β-arylpropanoic
acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the
enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were
compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding
energies than the designed acids, which makes them attractive target compounds for synthesis
and further examination., Neselektivni nesteroidni antiinflamatorni lekovi poput aspirina, ibuprofena i diklofenaka
inhibiraju enzime ciklooksigenazu-1 i ciklooksigenazu-2, a selektivni inhibitori ciljaju
ciklooksigenazu-2 koja je prekomerno izražena u inflamaciji, ali takođe i kod kancera,
ateroskleroze, Parkinsonove i Alchajmerove bolesti. Potencijalni kardiovaskularni i hepatički
neželjeni efekti selektivnih inhibitora ciklooksigenaze-2 su ograničili njihovu primenu. Razvoj
selektivnih i bezbednih inhibitora ciklooksigenaze-2 ostaje veoma prioritetna oblast u otkrivanju
lekova. Na osnovu strukture prethodno istraživanih novosintetisanih β-hidroksi-β-arilpropanskih
kiselina dizajnirane su dve grupe jedinjenja: analozi u kojima je jedan od benzenovih prstenova
zamenjen pirazolom, uz zadržavanje karboksilne grupe, i amidi β-hidroksi-β-arilpropanskih
kiselina sa pirazolom. Program AutoDock Vina 1.2.0 je korišćen za dokovanje dizajniranih
jedinjenja u 3D strukturu katalitičkog mesta enzima ciklooksigenaze-2, a ostvarene interakcije su
upoređene sa interakcijama koje ostvaruje selektivni inhibitor celekoksib. Amidi su imali nižu
energiju vezivanja od kiselina, što ih čini dobrim kandidatima za sintezu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site, Doking studije nekih jedinjenja sa pirazolom u aktivnom mestu ciklooksigenaze-2",
volume = "73",
number = "3",
pages = "205-215",
doi = "10.5937/arhfarm73-44720"
}

Savić, J., Antonijević, M., Crevar, M.,& Brborić, J.. (2023). Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 73(3), 205-215.
https://doi.org/10.5937/arhfarm73-44720

Savić J, Antonijević M, Crevar M, Brborić J. Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site. in Arhiv za farmaciju. 2023;73(3):205-215.
doi:10.5937/arhfarm73-44720 .

Savić, Jelena, Antonijević, Marija, Crevar, Milkica, Brborić, Jasmina, "Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site" in Arhiv za farmaciju, 73, no. 3 (2023):205-215,
https://doi.org/10.5937/arhfarm73-44720 . .

TY  - JOUR
AU  - Kotur-Stevuljević, Jelena
AU  - Savić, Jelena
AU  - Simić, Milena
AU  - Ivanišević, Jasmina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5014
AB  - Redox imbalance occurs when the factors of oxidative stress, known as prooxidants, outweigh
the mechanisms of antioxidant protection. In a healthy state, homeostatic mechanisms ensure the
balanced production of free radicals and a complete series of antioxidants responsible for their safe
removal. The generation of free radicals is a part of physiological processes in a healthy organism,
some of which act as specific signaling molecules, and their presence and activity are necessary in
these processes. In various diseases such as cancer, cardiovascular disease, diabetes, autoimmune
diseases, rheumatic diseases, systemic lupus, and skin diseases, the generation of free radicals
overwhelms the protective mechanisms, leading to the development of "oxidative stress" that damages
cells and tissues. To prevent the harmful effects of free radicals within cells, there exists a system of
enzymatic antioxidant protection composed of superoxide dismutase (SOD), glutathione peroxidase
(GSHPx), glutathione reductase (GR), glutaredoxin, reduced/oxidized glutathione (GSH/GSSG), and
thioredoxin (TRX). The examples of non-enzymatic antioxidants are: antioxidant vitamins such as A,
C and E, dihydrolypoic acid, metallothioneins, ceruloplasmin, coenzyme Q 10, urea, creatinine, etc.
Redox balance is influenced by the circadian rhythm and external factors that constitute the
"exposome", including dietary habits and lifestyle. Antioxidant supplementation has become
increasingly popular for maintaining optimal body function. However, it is important to note that some
antioxidants can exhibit prooxidant activity, emphasizing the need for controlled use. The relationship
between the redox status of the body and the action of antioxidants enables the development of
multidisciplinary research that connects biochemistry, molecular biology, nutritional science, natural
product chemistry, and clinical practice.
AB  - Redoks disbalans se javlja kada činioci oksidativnog stresa – prooksidansi – nadvladaju
mehanizme antioksidativne zaštite. U stanju zdravlja, homeostatski mehanizmi obezbeđuju
uravnoteženo stvaranje slobodnih radikala i čitave serije antioksidanasa koji su zaduženi za njihovo
bezbedno uklanjanje. Stvaranje slobodnih radikala je deo fizioloških procesa u zdravom organizmu;
neki od njih su specifični signalni molekuli i u tim procesima su njihovo prisustvo i aktivnost
neophodni. U različitim bolestima kao što su kancer, kardiovaskularne bolesti, dijabetes,
autoimunske bolesti, reumatske bolesti, sistemski lupus, kožne bolesti, stvaranje slobodnih radikala
nadvladava mehanizme zaštite, pa se razvija „oksidativni stres“ koji oštećuje ćelije i tkiva. Da bi se
sprečilo štetno delovanje slobodnih radikala, u ćeliji postoji sistem enzimske antioksidativne zaštite,
koga čine: superoksid-dismutaza (SOD), glutation-peroksidaza (GSHPx), glutation-reduktaza
(GR), glutaredoksin, redukovani/oksidovani glutation (GSH/GSSG) i tioredoksin (TRX). Primeri
neenzimskih antioksidanasa su: antioksidativni vitamini kao što su A, C i E, dihidrolipoinska
kiselina, metalotioneini, ceruloplazmin, koenzim Q10, urea, kreatinin, itd. Redoks ravnoteža je pod
uticajem cirkadijalnog ritma i spoljašnjih faktora koji čine „ekspozom“ i uključuju način ishrane i
životne navike. Suplementacija antioksidansima je postala sve popularnija praksa za održavanje
optimalne funkcije organizma. Neki od antioksidanasa ispoljavaju prooksidantnu aktivnost i zato je
važno da njihova primena bude kontrolisana. Veza između redoks statusa organizma i delovanja
antioksidanasa omogućava razvoj multidisciplinarnih istraživanja u kojima se povezuju biohemija,
molekularna biologija, nauka o ishrani, hemija prirodnih proizvoda i sama klinička praksa.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Redox homeostasis, oxidative stress and antioxidant system in health and disease: the possibility of modulation by antioxidants
T1  - Homeostaza redoks sistema, oksidativni stres i antioksidativni sistem u zdravlju i bolesti: mogućnost modulacije antioksidansima
VL  - 73
IS  - 4
SP  - 251
EP  - 263
DO  - 10.5937/arhfarm73-45369
ER  - 

@article{
author = "Kotur-Stevuljević, Jelena and Savić, Jelena and Simić, Milena and Ivanišević, Jasmina",
year = "2023",
abstract = "Redox imbalance occurs when the factors of oxidative stress, known as prooxidants, outweigh
the mechanisms of antioxidant protection. In a healthy state, homeostatic mechanisms ensure the
balanced production of free radicals and a complete series of antioxidants responsible for their safe
removal. The generation of free radicals is a part of physiological processes in a healthy organism,
some of which act as specific signaling molecules, and their presence and activity are necessary in
these processes. In various diseases such as cancer, cardiovascular disease, diabetes, autoimmune
diseases, rheumatic diseases, systemic lupus, and skin diseases, the generation of free radicals
overwhelms the protective mechanisms, leading to the development of "oxidative stress" that damages
cells and tissues. To prevent the harmful effects of free radicals within cells, there exists a system of
enzymatic antioxidant protection composed of superoxide dismutase (SOD), glutathione peroxidase
(GSHPx), glutathione reductase (GR), glutaredoxin, reduced/oxidized glutathione (GSH/GSSG), and
thioredoxin (TRX). The examples of non-enzymatic antioxidants are: antioxidant vitamins such as A,
C and E, dihydrolypoic acid, metallothioneins, ceruloplasmin, coenzyme Q 10, urea, creatinine, etc.
Redox balance is influenced by the circadian rhythm and external factors that constitute the
"exposome", including dietary habits and lifestyle. Antioxidant supplementation has become
increasingly popular for maintaining optimal body function. However, it is important to note that some
antioxidants can exhibit prooxidant activity, emphasizing the need for controlled use. The relationship
between the redox status of the body and the action of antioxidants enables the development of
multidisciplinary research that connects biochemistry, molecular biology, nutritional science, natural
product chemistry, and clinical practice., Redoks disbalans se javlja kada činioci oksidativnog stresa – prooksidansi – nadvladaju
mehanizme antioksidativne zaštite. U stanju zdravlja, homeostatski mehanizmi obezbeđuju
uravnoteženo stvaranje slobodnih radikala i čitave serije antioksidanasa koji su zaduženi za njihovo
bezbedno uklanjanje. Stvaranje slobodnih radikala je deo fizioloških procesa u zdravom organizmu;
neki od njih su specifični signalni molekuli i u tim procesima su njihovo prisustvo i aktivnost
neophodni. U različitim bolestima kao što su kancer, kardiovaskularne bolesti, dijabetes,
autoimunske bolesti, reumatske bolesti, sistemski lupus, kožne bolesti, stvaranje slobodnih radikala
nadvladava mehanizme zaštite, pa se razvija „oksidativni stres“ koji oštećuje ćelije i tkiva. Da bi se
sprečilo štetno delovanje slobodnih radikala, u ćeliji postoji sistem enzimske antioksidativne zaštite,
koga čine: superoksid-dismutaza (SOD), glutation-peroksidaza (GSHPx), glutation-reduktaza
(GR), glutaredoksin, redukovani/oksidovani glutation (GSH/GSSG) i tioredoksin (TRX). Primeri
neenzimskih antioksidanasa su: antioksidativni vitamini kao što su A, C i E, dihidrolipoinska
kiselina, metalotioneini, ceruloplazmin, koenzim Q10, urea, kreatinin, itd. Redoks ravnoteža je pod
uticajem cirkadijalnog ritma i spoljašnjih faktora koji čine „ekspozom“ i uključuju način ishrane i
životne navike. Suplementacija antioksidansima je postala sve popularnija praksa za održavanje
optimalne funkcije organizma. Neki od antioksidanasa ispoljavaju prooksidantnu aktivnost i zato je
važno da njihova primena bude kontrolisana. Veza između redoks statusa organizma i delovanja
antioksidanasa omogućava razvoj multidisciplinarnih istraživanja u kojima se povezuju biohemija,
molekularna biologija, nauka o ishrani, hemija prirodnih proizvoda i sama klinička praksa.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Redox homeostasis, oxidative stress and antioxidant system in health and disease: the possibility of modulation by antioxidants, Homeostaza redoks sistema, oksidativni stres i antioksidativni sistem u zdravlju i bolesti: mogućnost modulacije antioksidansima",
volume = "73",
number = "4",
pages = "251-263",
doi = "10.5937/arhfarm73-45369"
}

Kotur-Stevuljević, J., Savić, J., Simić, M.,& Ivanišević, J.. (2023). Redox homeostasis, oxidative stress and antioxidant system in health and disease: the possibility of modulation by antioxidants. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 73(4), 251-263.
https://doi.org/10.5937/arhfarm73-45369

Kotur-Stevuljević J, Savić J, Simić M, Ivanišević J. Redox homeostasis, oxidative stress and antioxidant system in health and disease: the possibility of modulation by antioxidants. in Arhiv za farmaciju. 2023;73(4):251-263.
doi:10.5937/arhfarm73-45369 .

Kotur-Stevuljević, Jelena, Savić, Jelena, Simić, Milena, Ivanišević, Jasmina, "Redox homeostasis, oxidative stress and antioxidant system in health and disease: the possibility of modulation by antioxidants" in Arhiv za farmaciju, 73, no. 4 (2023):251-263,
https://doi.org/10.5937/arhfarm73-45369 . .

TY  - JOUR
AU  - Subošić, Branko
AU  - Kotur-Stevuljević, Jelena
AU  - Brborić, Jasmina
AU  - Janković, Tamara
AU  - Milenković, Marina
AU  - Ivković, Branka
AU  - Kostadinović, Jelena
AU  - Savić, Jelena
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5146
AB  - The interplay between oxidative stress and inflammation is implicated in many chronic diseases including Alzheimer`s disease, cardiovascular diseases, diabetes and cancer. Thirteen β-hydroxy-β-arylalkanoic acids were previously synthesized and evaluated for their anti-inflammatory activity. The aim of this study was to asses ex vivo antioxidant activity of synthesized acids, as well as ibuprofen and to identify the compounds with the most promising results for further investigation on their capacity to counteract in vivo oxidative stress triggered by inflammation. The antioxidant potential of tested compounds was evaluated by determining the concentrations of total antioxidative status, total oxidative status, prooxidant antioxidant balance and the total sulfhydryl groups. Z score statistics were used to calculate the summary scores for antioxidative activity, prooxidative activity and oxy score. The tested compounds and ibuprofen demonstrated mild prooxidative activity ex vivo. Seven acids with substituents on one benzene ring exhibited better results than ibuprofen and were selected for in vivo testing. In vivo results demonstrated better antioxidant protection compared to ex vivo results. Compound g which contains nitro group on the benzene ring demonstrated the lowest oxy score, and four compounds exhibited better results than ibuprofen.
PB  - Pakistan Journal of Pharmaceutical Sciences
T2  - Pakistan Journal of Pharmaceutical Sciences
T1  - Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids
VL  - 36
IS  - 5
SP  - 1367
EP  - 1374
DO  - 10.36721/PJPS.2023.36.5.REG.1367-1374.1
ER  - 

@article{
author = "Subošić, Branko and Kotur-Stevuljević, Jelena and Brborić, Jasmina and Janković, Tamara and Milenković, Marina and Ivković, Branka and Kostadinović, Jelena and Savić, Jelena",
year = "2023",
abstract = "The interplay between oxidative stress and inflammation is implicated in many chronic diseases including Alzheimer`s disease, cardiovascular diseases, diabetes and cancer. Thirteen β-hydroxy-β-arylalkanoic acids were previously synthesized and evaluated for their anti-inflammatory activity. The aim of this study was to asses ex vivo antioxidant activity of synthesized acids, as well as ibuprofen and to identify the compounds with the most promising results for further investigation on their capacity to counteract in vivo oxidative stress triggered by inflammation. The antioxidant potential of tested compounds was evaluated by determining the concentrations of total antioxidative status, total oxidative status, prooxidant antioxidant balance and the total sulfhydryl groups. Z score statistics were used to calculate the summary scores for antioxidative activity, prooxidative activity and oxy score. The tested compounds and ibuprofen demonstrated mild prooxidative activity ex vivo. Seven acids with substituents on one benzene ring exhibited better results than ibuprofen and were selected for in vivo testing. In vivo results demonstrated better antioxidant protection compared to ex vivo results. Compound g which contains nitro group on the benzene ring demonstrated the lowest oxy score, and four compounds exhibited better results than ibuprofen.",
publisher = "Pakistan Journal of Pharmaceutical Sciences",
journal = "Pakistan Journal of Pharmaceutical Sciences",
title = "Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids",
volume = "36",
number = "5",
pages = "1367-1374",
doi = "10.36721/PJPS.2023.36.5.REG.1367-1374.1"
}

Subošić, B., Kotur-Stevuljević, J., Brborić, J., Janković, T., Milenković, M., Ivković, B., Kostadinović, J.,& Savić, J.. (2023). Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids. in Pakistan Journal of Pharmaceutical Sciences
Pakistan Journal of Pharmaceutical Sciences., 36(5), 1367-1374.
https://doi.org/10.36721/PJPS.2023.36.5.REG.1367-1374.1

Subošić B, Kotur-Stevuljević J, Brborić J, Janković T, Milenković M, Ivković B, Kostadinović J, Savić J. Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids. in Pakistan Journal of Pharmaceutical Sciences. 2023;36(5):1367-1374.
doi:10.36721/PJPS.2023.36.5.REG.1367-1374.1 .

Subošić, Branko, Kotur-Stevuljević, Jelena, Brborić, Jasmina, Janković, Tamara, Milenković, Marina, Ivković, Branka, Kostadinović, Jelena, Savić, Jelena, "Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids" in Pakistan Journal of Pharmaceutical Sciences, 36, no. 5 (2023):1367-1374,
https://doi.org/10.36721/PJPS.2023.36.5.REG.1367-1374.1 . .

TY  - JOUR
AU  - Džudović, Jelena
AU  - Crevar-Sakač, Milkica
AU  - Antunović, Marko
AU  - Repić, Aleksandra
AU  - Obradović, Slobodan
AU  - Đorđević, Snežana
AU  - Savić, Jelena
AU  - Džudović, Boris
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4332
AB  - Oral anticoagulants are a group of drugs used for the prevention and treatment of venous thrombosis and venous thromboembolism. For the last ten years, direct oral anticoagulants (DOAC) have been available and are equally effective, but significantly safer than vitamin K antagonists. In the case of an overdose, their most important side effect is still bleeding. Due to their widespread use, as well as increased toxicological importance there is a need to develop an analytical method for the determination of DOAC in biological material. The aim of this paper was to establish a method for the quantification of apixaban as one of the representatives of DOAC. The methodology of the study included the measurement of apixaban in the plasma of patients treated in the intensive care unit. Plasma apixaban concentrations were determined by LC-MS/MS technique using carbamazepine as an internal standard. Obtained validation parameters indicate that the introduced method is sensitive, reliable, precise and accurate. Using this method, apixaban can be quickly and easily detected and quantified in plasma in patients who are suspected of overdosing with this drug.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Development and validation of LC-MS/MS method for determination of plasma apixaban
VL  - 34
IS  - 3
SP  - 332
EP  - 337
DO  - 10.1556/1326.2021.00948
ER  - 

@article{
author = "Džudović, Jelena and Crevar-Sakač, Milkica and Antunović, Marko and Repić, Aleksandra and Obradović, Slobodan and Đorđević, Snežana and Savić, Jelena and Džudović, Boris",
year = "2022",
abstract = "Oral anticoagulants are a group of drugs used for the prevention and treatment of venous thrombosis and venous thromboembolism. For the last ten years, direct oral anticoagulants (DOAC) have been available and are equally effective, but significantly safer than vitamin K antagonists. In the case of an overdose, their most important side effect is still bleeding. Due to their widespread use, as well as increased toxicological importance there is a need to develop an analytical method for the determination of DOAC in biological material. The aim of this paper was to establish a method for the quantification of apixaban as one of the representatives of DOAC. The methodology of the study included the measurement of apixaban in the plasma of patients treated in the intensive care unit. Plasma apixaban concentrations were determined by LC-MS/MS technique using carbamazepine as an internal standard. Obtained validation parameters indicate that the introduced method is sensitive, reliable, precise and accurate. Using this method, apixaban can be quickly and easily detected and quantified in plasma in patients who are suspected of overdosing with this drug.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Development and validation of LC-MS/MS method for determination of plasma apixaban",
volume = "34",
number = "3",
pages = "332-337",
doi = "10.1556/1326.2021.00948"
}

Džudović, J., Crevar-Sakač, M., Antunović, M., Repić, A., Obradović, S., Đorđević, S., Savić, J.,& Džudović, B.. (2022). Development and validation of LC-MS/MS method for determination of plasma apixaban. in Acta Chromatographica
Akademiai Kiado ZRt.., 34(3), 332-337.
https://doi.org/10.1556/1326.2021.00948

Džudović J, Crevar-Sakač M, Antunović M, Repić A, Obradović S, Đorđević S, Savić J, Džudović B. Development and validation of LC-MS/MS method for determination of plasma apixaban. in Acta Chromatographica. 2022;34(3):332-337.
doi:10.1556/1326.2021.00948 .

Džudović, Jelena, Crevar-Sakač, Milkica, Antunović, Marko, Repić, Aleksandra, Obradović, Slobodan, Đorđević, Snežana, Savić, Jelena, Džudović, Boris, "Development and validation of LC-MS/MS method for determination of plasma apixaban" in Acta Chromatographica, 34, no. 3 (2022):332-337,
https://doi.org/10.1556/1326.2021.00948 . .

TY  - JOUR
AU  - Obradović, Darija
AU  - Savić, Jelena
AU  - Joksimović, J.
AU  - Kowalska, T.
AU  - Agbaba, Danica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4182
AB  - We investigated and compared hydrophilic retention mechanism (HILIC) of ten compounds (imidazoline and serotonin receptor ligands) in the thin-layer chromatographic (TLC) system and the high-performance liquid chromatographic (HPLC) system. The TLC and HPLC stationary phases were the chemically bonded amino (NH2) phases. In the TLC mode, the binary mobile phases were composed of acetonitrile (as the main component) and water or methanol (as the modifier). In the HPLC mode, the binary mobile phase was composed of acetonitrile (as the main component) and methanol (as the modifier). For each compound, we determined this region for which linear relationship between the retention and volume fraction of the mobile phase modifier was observed, and the retention behaviour was described by the linear solvent strength (LSS) model. With the obtained regression constant values (log k0, RM0) in mind, we selected molecular parameters influencing retention mechanism in the considered chromatographic systems. Lipophilicity plays an important role in the TLC mode with the acetonitrile‒methanol mobile phase, while geometrical characteristics of the test compounds (ring complexity, number of multiple bonds) play a predominant role in the TLC mode with the acetonitrile‒water mobile phase. It was also established that the hydrophilic mechanisms are different for the non-aqueous TLC vs. aqueous TLC systems and for the TLC vs. HPLC systems. As a result, different elution orders and separation performances can be expected for the imidazoline and serotonin receptor ligands, depending on the chromatographic system employed.
PB  - Springer
T2  - Journal of Planar Chromatography - Modern TLC
T1  - Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems
VL  - 35
IS  - 3
SP  - 251
EP  - 263
DO  - 10.1007/s00764-022-00172-6
ER  - 

@article{
author = "Obradović, Darija and Savić, Jelena and Joksimović, J. and Kowalska, T. and Agbaba, Danica",
year = "2022",
abstract = "We investigated and compared hydrophilic retention mechanism (HILIC) of ten compounds (imidazoline and serotonin receptor ligands) in the thin-layer chromatographic (TLC) system and the high-performance liquid chromatographic (HPLC) system. The TLC and HPLC stationary phases were the chemically bonded amino (NH2) phases. In the TLC mode, the binary mobile phases were composed of acetonitrile (as the main component) and water or methanol (as the modifier). In the HPLC mode, the binary mobile phase was composed of acetonitrile (as the main component) and methanol (as the modifier). For each compound, we determined this region for which linear relationship between the retention and volume fraction of the mobile phase modifier was observed, and the retention behaviour was described by the linear solvent strength (LSS) model. With the obtained regression constant values (log k0, RM0) in mind, we selected molecular parameters influencing retention mechanism in the considered chromatographic systems. Lipophilicity plays an important role in the TLC mode with the acetonitrile‒methanol mobile phase, while geometrical characteristics of the test compounds (ring complexity, number of multiple bonds) play a predominant role in the TLC mode with the acetonitrile‒water mobile phase. It was also established that the hydrophilic mechanisms are different for the non-aqueous TLC vs. aqueous TLC systems and for the TLC vs. HPLC systems. As a result, different elution orders and separation performances can be expected for the imidazoline and serotonin receptor ligands, depending on the chromatographic system employed.",
publisher = "Springer",
journal = "Journal of Planar Chromatography - Modern TLC",
title = "Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems",
volume = "35",
number = "3",
pages = "251-263",
doi = "10.1007/s00764-022-00172-6"
}

Obradović, D., Savić, J., Joksimović, J., Kowalska, T.,& Agbaba, D.. (2022). Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems. in Journal of Planar Chromatography - Modern TLC
Springer., 35(3), 251-263.
https://doi.org/10.1007/s00764-022-00172-6

Obradović D, Savić J, Joksimović J, Kowalska T, Agbaba D. Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems. in Journal of Planar Chromatography - Modern TLC. 2022;35(3):251-263.
doi:10.1007/s00764-022-00172-6 .

Obradović, Darija, Savić, Jelena, Joksimović, J., Kowalska, T., Agbaba, Danica, "Hydrophilic retention mechanism of imidazoline and serotonin receptor ligands in thin-layer and high-performance liquid chromatography systems" in Journal of Planar Chromatography - Modern TLC, 35, no. 3 (2022):251-263,
https://doi.org/10.1007/s00764-022-00172-6 . .

TY  - CONF
AU  - Savić, Jelena
AU  - Brborić, Jasmina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4445
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for nearly a century
for alleviation of symptoms of acute and chronic inflammation and represent one of the most
used groups of drugs in the general population. NSAIDs group is very numerous and it
includes different chemical structures. The main mechanism of action of these drugs is the
inhibition of enzyme cyclooxygenase (COX) which catalyzes prostaglandin production (of
which some are inflammatory mediators) from arachidonic acid and depending on whether
they inhibit both isoforms (COX-1 and COX-2) and just COX-2 they can be classified as
nonselective and selective. The need for finding the new NSAIDs with fewer side effects is
still persistent because nonselective NSAIDs often cause gastrointestinal side effects which
vary from mild to very serious like bleeding, while some selective are withdrawn because of
serious cardiovascular side effects with death outcome (1). Several epidemiologic studies
have shown a negative correlation between NSAID use and the occurrence of Alzheimer`s
disease, as well as some types of cancer, particularly colorectal and breast cancer. The
development of compounds that would be used in Alzheimer`s disease therapy is direct on
structures that exhibit more effects at the same time, one of which is anti-inflammatory
effect mediated via COX-2 inhibition. Although chemoprevention mechanisms are not
completely delineated, it is indisputable that both COX isoforms play a role in carcinogenesis,
and these findings opened a new field of research for the design and synthesis of new COX
inhibitors with chemoprotective, antiangiogenic, and cytotoxic activity.
AB  - Nesteroidni antiinflamatorni lekovi (NSAIL) se koriste za ublažavanje simptoma
akutne i hronične inflamacije već skoro čitav vek i predstavljaju jednu od najčešće
primenjivanih grupa lekova u najširoj populaciji. Grupa NSAIL je veoma brojna i obuhvata
različite hemijske strukture. Glavni mehanizam delovanja ovih lekova je inhibicija enzima
ciklooksigenaze (COX) koji katalizuje produkciju prostaglandina (od kojih su neki medijatori
inflamacije) iz arahidonske kiseline, a u zavisnosti od toga da li inhibiraju obe izoforme
(COX-1 i COX-2) ili samo COX-2, dele se na neselektivne i selektivne. Potreba za otkrivanjem
novih NSAIL sa manje neželjenih efekata je i danas aktuelna, jer neselektivni NSAIL često
izazivaju neželjene gastrointestinalne efekte koji variraju od blagih do veoma ozbiljnih kao
što je krvarenje, a neki selektivni lekovi su povučeni iz upotrebe zbog ozbiljnih neželjenih
kardiovaskularnih efekata sa smrtnim ishodom (1). Nekoliko epidemioloških studija je
pokazalo da postoji negativna korelacija između upotrebe NSAIL i pojave Alchajmerove
bolesti, kao i nekih tipova kancera, a naročito kolorektalnog i kancera dojke. Razvoj
jedinjenja koja bi se koristila u terapiji Alchajmerove bolesti je usmeren na strukture koje
istovremeno imaju više efekata, a jedan od njih je antiinflamatorni posredovan inhibicijom
COX-2. Iako mehanizmi hemoprevencije nisu potpuno rasvetljeni, nesporno je da postoji
uloga obe COX izoforme u karcinogenezi, a ova saznanja su otvorila novo polje istraživanja ka
dizajniranju i sintezi novih COX inhibitora sa hemoprotektivnom, antiangiogeneznom i
citotoksičnom aktivnošću.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - New directions in the development of cyclooxygenase inhibitors
T1  - Novi pravci u razvoju inhibitora ciklooksigenaze
VL  - 72
IS  - 4 suplement
SP  - S53
EP  - S54
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4445
ER  - 

@conference{
author = "Savić, Jelena and Brborić, Jasmina",
year = "2022",
abstract = "Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for nearly a century
for alleviation of symptoms of acute and chronic inflammation and represent one of the most
used groups of drugs in the general population. NSAIDs group is very numerous and it
includes different chemical structures. The main mechanism of action of these drugs is the
inhibition of enzyme cyclooxygenase (COX) which catalyzes prostaglandin production (of
which some are inflammatory mediators) from arachidonic acid and depending on whether
they inhibit both isoforms (COX-1 and COX-2) and just COX-2 they can be classified as
nonselective and selective. The need for finding the new NSAIDs with fewer side effects is
still persistent because nonselective NSAIDs often cause gastrointestinal side effects which
vary from mild to very serious like bleeding, while some selective are withdrawn because of
serious cardiovascular side effects with death outcome (1). Several epidemiologic studies
have shown a negative correlation between NSAID use and the occurrence of Alzheimer`s
disease, as well as some types of cancer, particularly colorectal and breast cancer. The
development of compounds that would be used in Alzheimer`s disease therapy is direct on
structures that exhibit more effects at the same time, one of which is anti-inflammatory
effect mediated via COX-2 inhibition. Although chemoprevention mechanisms are not
completely delineated, it is indisputable that both COX isoforms play a role in carcinogenesis,
and these findings opened a new field of research for the design and synthesis of new COX
inhibitors with chemoprotective, antiangiogenic, and cytotoxic activity., Nesteroidni antiinflamatorni lekovi (NSAIL) se koriste za ublažavanje simptoma
akutne i hronične inflamacije već skoro čitav vek i predstavljaju jednu od najčešće
primenjivanih grupa lekova u najširoj populaciji. Grupa NSAIL je veoma brojna i obuhvata
različite hemijske strukture. Glavni mehanizam delovanja ovih lekova je inhibicija enzima
ciklooksigenaze (COX) koji katalizuje produkciju prostaglandina (od kojih su neki medijatori
inflamacije) iz arahidonske kiseline, a u zavisnosti od toga da li inhibiraju obe izoforme
(COX-1 i COX-2) ili samo COX-2, dele se na neselektivne i selektivne. Potreba za otkrivanjem
novih NSAIL sa manje neželjenih efekata je i danas aktuelna, jer neselektivni NSAIL često
izazivaju neželjene gastrointestinalne efekte koji variraju od blagih do veoma ozbiljnih kao
što je krvarenje, a neki selektivni lekovi su povučeni iz upotrebe zbog ozbiljnih neželjenih
kardiovaskularnih efekata sa smrtnim ishodom (1). Nekoliko epidemioloških studija je
pokazalo da postoji negativna korelacija između upotrebe NSAIL i pojave Alchajmerove
bolesti, kao i nekih tipova kancera, a naročito kolorektalnog i kancera dojke. Razvoj
jedinjenja koja bi se koristila u terapiji Alchajmerove bolesti je usmeren na strukture koje
istovremeno imaju više efekata, a jedan od njih je antiinflamatorni posredovan inhibicijom
COX-2. Iako mehanizmi hemoprevencije nisu potpuno rasvetljeni, nesporno je da postoji
uloga obe COX izoforme u karcinogenezi, a ova saznanja su otvorila novo polje istraživanja ka
dizajniranju i sintezi novih COX inhibitora sa hemoprotektivnom, antiangiogeneznom i
citotoksičnom aktivnošću.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "New directions in the development of cyclooxygenase inhibitors, Novi pravci u razvoju inhibitora ciklooksigenaze",
volume = "72",
number = "4 suplement",
pages = "S53-S54",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4445"
}

Savić, J.,& Brborić, J.. (2022). New directions in the development of cyclooxygenase inhibitors. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S53-S54.
https://hdl.handle.net/21.15107/rcub_farfar_4445

Savić J, Brborić J. New directions in the development of cyclooxygenase inhibitors. in Arhiv za farmaciju. 2022;72(4 suplement):S53-S54.
https://hdl.handle.net/21.15107/rcub_farfar_4445 .

Savić, Jelena, Brborić, Jasmina, "New directions in the development of cyclooxygenase inhibitors" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S53-S54,
https://hdl.handle.net/21.15107/rcub_farfar_4445 .

TY  - CONF
AU  - Obradović, Darija
AU  - Savić, Jelena
AU  - Joksimović, Jovana
AU  - Marković, Bojan
AU  - Vujić, Zorica
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4605
AB  - The serotonin receptor ligands, such as structurally related arylpiperazine and
benzothiazepine derivatives, are most commonly used in the treatment of schizophrenia,
depression, and manic disorders. (1). Due to emphasized lipophilicity, their retention can be
successfully defined under the reversed-phase (RP) chromatographic conditions. Using the
experimental design methodology (2), the retention of selected serotonin receptor ligands
(aripiprazole, ziprasidone, risperidone, olanzapine, quetiapine, mirtazapine) was tested on
RP stationary phases, in order to define differences in their retention mechanisms and
ensure the further optimization of separation conditions. The silica modified, C8 and
pentafluorophenylpropyl (PFP) columns were used as stationary phases, while the mobile
phase was a mixture of acetonitrile and ammonium acetate. The experimental plan was
defined according to the central composite design varying the following factors: ammonium
acetate concentration (15-25 mM), volume fraction of acetonitrile (40-50% v/v), and column
temperature (20-30°C). The differences between retention on C8 and PFP columns were
presented by using the radar plots and principal component analysis. The obtained
differences are especially visible in the case of ziprasidone, olanzapine, quetiapine and
mirtazapine, which may explain the occurrence of inversions in their elution order. On C8
phase the separation of structurally related arylpiperazine or benzothiazepine derivatives
was achieved, while the PFP phase showed more successful applicability in the separation of
all tested ligands. The slightly higher values of the selectivity parameter were obtained for
40% of acetonitrile in the mobile phase. In further optimization of the separation conditions,
the PFP bonded stationary phase can be successfully applied.
AB  - Ligandi serotoninskih receptora kao što su strukturno srodni derivati arilpiperazina i
benzotiazepina, najčešće se koriste u terapiji oboljenja centralnog nervnog sistema, poput
šizofrenije, depresije, ili maničnog poremećaja (1). Zbog izraženih lipofilnih karakteristika,
njihovo retenciono ponašanje se može uspešno definisati u uslovima reverzno-fazne
(Reversed‐Phase, RP) tečne hromatografije. Primenom metodologije eksperimentalnog
dizajna (2), retencione karakteristike odabranih liganada serotoninskih receptora
(aripiprazol, ziprazidon, risperidon, olanzapin, kvetiapin, mirtazapin) su ispitane na RP
stacionarnim fazama, sa ciljem definisanja razlika u mehanizmima zadržavanja i daljoj
optimizaciji hromatografskih uslova razdvajanja. Kao stacionarne faze korišćene su C8 i
pentafluorofenilpropil (PFP) kolone, dok je mobilna faza bila smeša acetonitrila i amonijum-
acetata. Plan izvođenja eksperimenta je postavljen prema planu centralnog kompozitnog
dizajna variranjem sledećih hromatografskih faktora: koncentracije amonijum-acetata (15-
25 mM), zapreminskog udela acetonitrila (40-50% v/v) i temperature kolone (20-30°C).
Primenom linearne regresione analize, definisan je uticaj izabranih faktora na promenu
retencionog ponašanja (k) ispitivanih liganada. Korišćenjem radar grafika i primenom
analize glavnih komponenti predstavljene su razlike između mehanizama zadržavanja na C8
i PFP kolonama. Razlike su posebno vidljive u slučaju ziprazidona, olanzapina, kvetiapina i
mirtazapina čime se može objasniti inverzija u njihovom redosledu eluiranja. Uočeno je da
C8 stacionarna faza pogoduje razdvajanju strukturno srodnih arilpiperazina ili strukturno
srodnih derivata benzotiazepina, dok je PFP stacionarna faza pokazala uspešniju
primenljivost u razdvajanju svih ispitivanih liganada. Nešto veće vrednosti parametra
selektivnosti dobijene su na 40% udelu acetonitrila u mobilnoj fazi. U daljoj optimizaciji
hromatografskih uslova razdvajanja ispitivanih liganada, stacionarna faza sa vezanim PFP
grupama se može uspešno primeniti.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography
T1  - Ptimizacija reverzno‐faznih uslova za razdvajanje liganada serotoninskih receptora u tečnoj hromatografiji
VL  - 72
IS  - 4 suplement
SP  - S548
EP  - S549
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4605
ER  - 

@conference{
author = "Obradović, Darija and Savić, Jelena and Joksimović, Jovana and Marković, Bojan and Vujić, Zorica",
year = "2022",
abstract = "The serotonin receptor ligands, such as structurally related arylpiperazine and
benzothiazepine derivatives, are most commonly used in the treatment of schizophrenia,
depression, and manic disorders. (1). Due to emphasized lipophilicity, their retention can be
successfully defined under the reversed-phase (RP) chromatographic conditions. Using the
experimental design methodology (2), the retention of selected serotonin receptor ligands
(aripiprazole, ziprasidone, risperidone, olanzapine, quetiapine, mirtazapine) was tested on
RP stationary phases, in order to define differences in their retention mechanisms and
ensure the further optimization of separation conditions. The silica modified, C8 and
pentafluorophenylpropyl (PFP) columns were used as stationary phases, while the mobile
phase was a mixture of acetonitrile and ammonium acetate. The experimental plan was
defined according to the central composite design varying the following factors: ammonium
acetate concentration (15-25 mM), volume fraction of acetonitrile (40-50% v/v), and column
temperature (20-30°C). The differences between retention on C8 and PFP columns were
presented by using the radar plots and principal component analysis. The obtained
differences are especially visible in the case of ziprasidone, olanzapine, quetiapine and
mirtazapine, which may explain the occurrence of inversions in their elution order. On C8
phase the separation of structurally related arylpiperazine or benzothiazepine derivatives
was achieved, while the PFP phase showed more successful applicability in the separation of
all tested ligands. The slightly higher values of the selectivity parameter were obtained for
40% of acetonitrile in the mobile phase. In further optimization of the separation conditions,
the PFP bonded stationary phase can be successfully applied., Ligandi serotoninskih receptora kao što su strukturno srodni derivati arilpiperazina i
benzotiazepina, najčešće se koriste u terapiji oboljenja centralnog nervnog sistema, poput
šizofrenije, depresije, ili maničnog poremećaja (1). Zbog izraženih lipofilnih karakteristika,
njihovo retenciono ponašanje se može uspešno definisati u uslovima reverzno-fazne
(Reversed‐Phase, RP) tečne hromatografije. Primenom metodologije eksperimentalnog
dizajna (2), retencione karakteristike odabranih liganada serotoninskih receptora
(aripiprazol, ziprazidon, risperidon, olanzapin, kvetiapin, mirtazapin) su ispitane na RP
stacionarnim fazama, sa ciljem definisanja razlika u mehanizmima zadržavanja i daljoj
optimizaciji hromatografskih uslova razdvajanja. Kao stacionarne faze korišćene su C8 i
pentafluorofenilpropil (PFP) kolone, dok je mobilna faza bila smeša acetonitrila i amonijum-
acetata. Plan izvođenja eksperimenta je postavljen prema planu centralnog kompozitnog
dizajna variranjem sledećih hromatografskih faktora: koncentracije amonijum-acetata (15-
25 mM), zapreminskog udela acetonitrila (40-50% v/v) i temperature kolone (20-30°C).
Primenom linearne regresione analize, definisan je uticaj izabranih faktora na promenu
retencionog ponašanja (k) ispitivanih liganada. Korišćenjem radar grafika i primenom
analize glavnih komponenti predstavljene su razlike između mehanizama zadržavanja na C8
i PFP kolonama. Razlike su posebno vidljive u slučaju ziprazidona, olanzapina, kvetiapina i
mirtazapina čime se može objasniti inverzija u njihovom redosledu eluiranja. Uočeno je da
C8 stacionarna faza pogoduje razdvajanju strukturno srodnih arilpiperazina ili strukturno
srodnih derivata benzotiazepina, dok je PFP stacionarna faza pokazala uspešniju
primenljivost u razdvajanju svih ispitivanih liganada. Nešto veće vrednosti parametra
selektivnosti dobijene su na 40% udelu acetonitrila u mobilnoj fazi. U daljoj optimizaciji
hromatografskih uslova razdvajanja ispitivanih liganada, stacionarna faza sa vezanim PFP
grupama se može uspešno primeniti.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography, Ptimizacija reverzno‐faznih uslova za razdvajanje liganada serotoninskih receptora u tečnoj hromatografiji",
volume = "72",
number = "4 suplement",
pages = "S548-S549",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4605"
}

Obradović, D., Savić, J., Joksimović, J., Marković, B.,& Vujić, Z.. (2022). Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S548-S549.
https://hdl.handle.net/21.15107/rcub_farfar_4605

Obradović D, Savić J, Joksimović J, Marković B, Vujić Z. Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography. in Arhiv za farmaciju. 2022;72(4 suplement):S548-S549.
https://hdl.handle.net/21.15107/rcub_farfar_4605 .

Obradović, Darija, Savić, Jelena, Joksimović, Jovana, Marković, Bojan, Vujić, Zorica, "Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S548-S549,
https://hdl.handle.net/21.15107/rcub_farfar_4605 .

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  - 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  - JOUR
AU  - Savić, Jelena
AU  - Dilber, Sanda
AU  - Crevar-Sakač, Milkica
AU  - Vladimirov, Sote
AU  - Brborić, Jasmina
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3096
AB  - Lipophilicity parameters (logP) were determined for thirteen synthesized β-hydroxy-β-arilalkanoic acids using reversed phase high performance liquid chromatography. Anti-inflammatory activity and potential selectivity towards cyclooxygenase-2 inhibition of synthetized compounds was assessed. Stationary phase was octadecyl modified (C-18) silicagel, and four used mobile phases contained different amount of methanol. Both synthetized and standard compounds with known logP values (aspirin, ibuprofen, ketoprofen, naproxen and phenanthrene) were tested in a chromatographic system. Using retention times for each standard and synthesized compound logk values (logarithm of capacity factor) were calculated. Intercept on a graph showing dependency of logk from methanol amount in the mobile phase for each compound represents logKw(capacity factor when organic solvent amount is zero). Graph showing linear dependency of logP of standard compounds from experimentally obtained logKw values was plotted. LogP values for synthetized compounds were obtained by interpolation from the plotted graph. Obtained values are in a range from 2.901 to 3.847. The best correlation between experimentally obtained and predicted logP values was using KOWWIN software (R2=0.8864), which makes this software appropriate for predicting logP values of this type of compounds.
AB  - Parametri lipofilnosti (logP) su određeni za trinaest sintetisanih β-hidroksi-β-arilalkanskih kiselina primenom reverzno fazne tečne hromatografije. Ispitivanje je urađeno na derivatima kojima je tokom prethodnih istraživanja okarakterisana antiinflamatorna aktivnost i pretpostavljena je potencijalna selektivnost prema inhibiciji ciklooksigenaze-2. Oktadecil-modifikovani (C-18) silikagel je predstavljao stacionarnu fazu, a korišćene su četiri mobilne faze u kojima je variran udeo metanola. Hromatografski su testirana jedinjenja sa poznatim logP vrednostima (aspirin, ibuprofen, ketoprofen, naproksen i fenantren) i sintetisana jedinjenja. Na osnovu retencionog vremena za svako standardno i sintetisano jedinjenje izračunate su vrednosti logk (logaritam faktora kapaciteta). Odsečak na y osi grafika zavisnosti logk od udela metanola u mobilnoj fazi za svako jedinjenje predstavlja vrednost logKw (vrednost retencionog faktora za hromatografski sistem u kome je sadržaj organske komponente nula) za dato jedinjenje. Konstruisan je grafik zavisnosti logP za standardna jedinjenja od njihovih eksperimentalno dobijenih logKw vrednosti i uspostavljena je linearna zavisnost. Interpolacijom logKw sa grafika su očitane vrednosti logP za sintetisana jedinjenja. Dobijene vrednosti su u opsegu od 2,901 do 3,847. Za predviđanje logP vrednosti korišćeni su računarski programi: AlogPS, Molinspiration, MarvinSketch i KOWWIN. Najbolja korelacija između eksperimentalno određenih i predviđenih rezultata je u programu KOWWIN (R2=0,8864), što čini ovaj program pogodnim za predviđanje logP vrednosti ovog tipa jedinjenja.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure
T1  - Određivanje lipofilnosti β-hidroksi-β-arilalkanskih kiselina primenom reverzno-fazne tečne hromatografije pod visokim pritiskom
VL  - 68
IS  - 1
SP  - 34
EP  - 45
DO  - 10.5937/arhFarm1801034S
ER  - 

@article{
author = "Savić, Jelena and Dilber, Sanda and Crevar-Sakač, Milkica and Vladimirov, Sote and Brborić, Jasmina",
year = "2018",
abstract = "Lipophilicity parameters (logP) were determined for thirteen synthesized β-hydroxy-β-arilalkanoic acids using reversed phase high performance liquid chromatography. Anti-inflammatory activity and potential selectivity towards cyclooxygenase-2 inhibition of synthetized compounds was assessed. Stationary phase was octadecyl modified (C-18) silicagel, and four used mobile phases contained different amount of methanol. Both synthetized and standard compounds with known logP values (aspirin, ibuprofen, ketoprofen, naproxen and phenanthrene) were tested in a chromatographic system. Using retention times for each standard and synthesized compound logk values (logarithm of capacity factor) were calculated. Intercept on a graph showing dependency of logk from methanol amount in the mobile phase for each compound represents logKw(capacity factor when organic solvent amount is zero). Graph showing linear dependency of logP of standard compounds from experimentally obtained logKw values was plotted. LogP values for synthetized compounds were obtained by interpolation from the plotted graph. Obtained values are in a range from 2.901 to 3.847. The best correlation between experimentally obtained and predicted logP values was using KOWWIN software (R2=0.8864), which makes this software appropriate for predicting logP values of this type of compounds., Parametri lipofilnosti (logP) su određeni za trinaest sintetisanih β-hidroksi-β-arilalkanskih kiselina primenom reverzno fazne tečne hromatografije. Ispitivanje je urađeno na derivatima kojima je tokom prethodnih istraživanja okarakterisana antiinflamatorna aktivnost i pretpostavljena je potencijalna selektivnost prema inhibiciji ciklooksigenaze-2. Oktadecil-modifikovani (C-18) silikagel je predstavljao stacionarnu fazu, a korišćene su četiri mobilne faze u kojima je variran udeo metanola. Hromatografski su testirana jedinjenja sa poznatim logP vrednostima (aspirin, ibuprofen, ketoprofen, naproksen i fenantren) i sintetisana jedinjenja. Na osnovu retencionog vremena za svako standardno i sintetisano jedinjenje izračunate su vrednosti logk (logaritam faktora kapaciteta). Odsečak na y osi grafika zavisnosti logk od udela metanola u mobilnoj fazi za svako jedinjenje predstavlja vrednost logKw (vrednost retencionog faktora za hromatografski sistem u kome je sadržaj organske komponente nula) za dato jedinjenje. Konstruisan je grafik zavisnosti logP za standardna jedinjenja od njihovih eksperimentalno dobijenih logKw vrednosti i uspostavljena je linearna zavisnost. Interpolacijom logKw sa grafika su očitane vrednosti logP za sintetisana jedinjenja. Dobijene vrednosti su u opsegu od 2,901 do 3,847. Za predviđanje logP vrednosti korišćeni su računarski programi: AlogPS, Molinspiration, MarvinSketch i KOWWIN. Najbolja korelacija između eksperimentalno određenih i predviđenih rezultata je u programu KOWWIN (R2=0,8864), što čini ovaj program pogodnim za predviđanje logP vrednosti ovog tipa jedinjenja.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure, Određivanje lipofilnosti β-hidroksi-β-arilalkanskih kiselina primenom reverzno-fazne tečne hromatografije pod visokim pritiskom",
volume = "68",
number = "1",
pages = "34-45",
doi = "10.5937/arhFarm1801034S"
}

Savić, J., Dilber, S., Crevar-Sakač, M., Vladimirov, S.,& Brborić, J.. (2018). Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 68(1), 34-45.
https://doi.org/10.5937/arhFarm1801034S

Savić J, Dilber S, Crevar-Sakač M, Vladimirov S, Brborić J. Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure. in Arhiv za farmaciju. 2018;68(1):34-45.
doi:10.5937/arhFarm1801034S .

Savić, Jelena, Dilber, Sanda, Crevar-Sakač, Milkica, Vladimirov, Sote, Brborić, Jasmina, "Lipophilicity determination of β-hydroxy-β-arilalkanoic acids by reversed phase liquid chromatography under high pressure" in Arhiv za farmaciju, 68, no. 1 (2018):34-45,
https://doi.org/10.5937/arhFarm1801034S . .

TY  - JOUR
AU  - Savić, Jelena
AU  - Dilber, Sanda
AU  - Vujić, Zorica
AU  - Vladimirov, Sote
AU  - Brborić, Jasmina
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3069
AB  - The pK(a) values of twelve beta-hydroxy-beta-arylalkanoic acids and ibuprofen were determined using a modified RP-HPLC method. The stationary phase was octadecyl modified (C-18) silica gel, and the mobile phases were mixtures of methanol and one of ten different buffers (60: 40 volume ratio). The mean retention time of each compound was plotted against the pH of each of the ten used mobile phases. The inflection point of the obtained sigmoidal curve represents the (s)(w)pK(a) of a compound. Using (s)(w)pKa in previously established equations for the specific methanol/buffer mixture, the (w)(w)pK(a) values (in pure water) were calculated. The obtained wwpKa values for the synthesized compounds were in a range from 3.40 to 3.74, and the (w)(w)pK(a) for ibuprofen was 4.27. The Predicted pK(a) values for this type of compounds in the MarvinSketch 5.11.5. Program were in poor correlation with the experimental results, while in ACD//I-Labs pK(a) values were calculated as a wide range.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - A modified RP-HPLC method for the determination of the pK(a) values of synthesized beta-hydroxy-beta-arylalkanoic acids
VL  - 83
IS  - 7-8
SP  - 875
EP  - 883
DO  - 10.2298/JSC170804045S
ER  - 

@article{
author = "Savić, Jelena and Dilber, Sanda and Vujić, Zorica and Vladimirov, Sote and Brborić, Jasmina",
year = "2018",
abstract = "The pK(a) values of twelve beta-hydroxy-beta-arylalkanoic acids and ibuprofen were determined using a modified RP-HPLC method. The stationary phase was octadecyl modified (C-18) silica gel, and the mobile phases were mixtures of methanol and one of ten different buffers (60: 40 volume ratio). The mean retention time of each compound was plotted against the pH of each of the ten used mobile phases. The inflection point of the obtained sigmoidal curve represents the (s)(w)pK(a) of a compound. Using (s)(w)pKa in previously established equations for the specific methanol/buffer mixture, the (w)(w)pK(a) values (in pure water) were calculated. The obtained wwpKa values for the synthesized compounds were in a range from 3.40 to 3.74, and the (w)(w)pK(a) for ibuprofen was 4.27. The Predicted pK(a) values for this type of compounds in the MarvinSketch 5.11.5. Program were in poor correlation with the experimental results, while in ACD//I-Labs pK(a) values were calculated as a wide range.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "A modified RP-HPLC method for the determination of the pK(a) values of synthesized beta-hydroxy-beta-arylalkanoic acids",
volume = "83",
number = "7-8",
pages = "875-883",
doi = "10.2298/JSC170804045S"
}

Savić, J., Dilber, S., Vujić, Z., Vladimirov, S.,& Brborić, J.. (2018). A modified RP-HPLC method for the determination of the pK(a) values of synthesized beta-hydroxy-beta-arylalkanoic acids. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 83(7-8), 875-883.
https://doi.org/10.2298/JSC170804045S

Savić J, Dilber S, Vujić Z, Vladimirov S, Brborić J. A modified RP-HPLC method for the determination of the pK(a) values of synthesized beta-hydroxy-beta-arylalkanoic acids. in Journal of the Serbian Chemical Society. 2018;83(7-8):875-883.
doi:10.2298/JSC170804045S .

Savić, Jelena, Dilber, Sanda, Vujić, Zorica, Vladimirov, Sote, Brborić, Jasmina, "A modified RP-HPLC method for the determination of the pK(a) values of synthesized beta-hydroxy-beta-arylalkanoic acids" in Journal of the Serbian Chemical Society, 83, no. 7-8 (2018):875-883,
https://doi.org/10.2298/JSC170804045S . .

TY  - JOUR
AU  - Savić, Jelena
AU  - Marković, Bojan
AU  - Vitnik, Vesna
AU  - Dilber, Sanda
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3032
AB  - pKa values of five β-hydroxy-β-arylalkanoic acids and ibuprofen were determined using the RP-HPLC method. Stationary phase was octadecyl modified (C-18) silica gel, and mobile phase was a mixture of methanol and one of nine different buffers (60:40, v/v). wspH values were measured after mixing methanol with an appropriate buffer. The mean retention time of each compound was plotted against wspH of each mobile phase. The inflection point of each sigmoidal curve represented wspK a of the compound. Using wspK a in already known equations for the specific methanol/buffer mixture, wwpK a values were calculated. Obtained pKa values for synthesized compounds were in a narrow range from 3.34-3.81 and pKa for ibuprofen was 4.45. Predicted pKa values for these compounds in SPARC software showed good correlation with experimental pKa values (R2=0.8048).
PB  - Univerzitet u Kragujevcu - Prirodno-matematički fakultet, Kragujevac
T2  - Kragujevac Journal of Science
T1  - Determination of ionization constants (PKA) of β-hydroxy-β-arylalkanoic acids using high-pressure liquid chromatography
IS  - 40
SP  - 103
EP  - 111
DO  - 10.5937/KgJSci1840103S
ER  - 

@article{
author = "Savić, Jelena and Marković, Bojan and Vitnik, Vesna and Dilber, Sanda",
year = "2018",
abstract = "pKa values of five β-hydroxy-β-arylalkanoic acids and ibuprofen were determined using the RP-HPLC method. Stationary phase was octadecyl modified (C-18) silica gel, and mobile phase was a mixture of methanol and one of nine different buffers (60:40, v/v). wspH values were measured after mixing methanol with an appropriate buffer. The mean retention time of each compound was plotted against wspH of each mobile phase. The inflection point of each sigmoidal curve represented wspK a of the compound. Using wspK a in already known equations for the specific methanol/buffer mixture, wwpK a values were calculated. Obtained pKa values for synthesized compounds were in a narrow range from 3.34-3.81 and pKa for ibuprofen was 4.45. Predicted pKa values for these compounds in SPARC software showed good correlation with experimental pKa values (R2=0.8048).",
publisher = "Univerzitet u Kragujevcu - Prirodno-matematički fakultet, Kragujevac",
journal = "Kragujevac Journal of Science",
title = "Determination of ionization constants (PKA) of β-hydroxy-β-arylalkanoic acids using high-pressure liquid chromatography",
number = "40",
pages = "103-111",
doi = "10.5937/KgJSci1840103S"
}

Savić, J., Marković, B., Vitnik, V.,& Dilber, S.. (2018). Determination of ionization constants (PKA) of β-hydroxy-β-arylalkanoic acids using high-pressure liquid chromatography. in Kragujevac Journal of Science
Univerzitet u Kragujevcu - Prirodno-matematički fakultet, Kragujevac.(40), 103-111.
https://doi.org/10.5937/KgJSci1840103S

Savić J, Marković B, Vitnik V, Dilber S. Determination of ionization constants (PKA) of β-hydroxy-β-arylalkanoic acids using high-pressure liquid chromatography. in Kragujevac Journal of Science. 2018;(40):103-111.
doi:10.5937/KgJSci1840103S .

Savić, Jelena, Marković, Bojan, Vitnik, Vesna, Dilber, Sanda, "Determination of ionization constants (PKA) of β-hydroxy-β-arylalkanoic acids using high-pressure liquid chromatography" in Kragujevac Journal of Science, no. 40 (2018):103-111,
https://doi.org/10.5937/KgJSci1840103S . .

TY  - THES
AU  - Savić, Jelena
PY  - 2017
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=5319
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:16553/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=49496847
UR  - http://nardus.mpn.gov.rs/123456789/8783
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3409
AB  - Nesteroidni antiinflamatorni lekovi (NSAIL) se koriste za ublažavanje simptomaakutne i hronične inflamacije već više od pedeset godina. Grupa NSAIL je veomabrojna i obuhvata različite hemijske strukture. Potreba za pronalaženjem novih NSAIL idalje postoji jer neselektivni NSAIL često izazivaju neželjene gastrointestinalne efekte,a neki noviji selektivni lekovi se dovode u vezu sa ozbiljnim neželjenimkardiovaskularnim efektima.U ovoj disertaciji opisani su dizajniranje, sinteza, ispitivanje fizičko-hemijskih ibioloških osobina β-hidroksi-β-arilalkanskih kiselina. U doking studijama je ispitanuticaj α supstitucije jednom ili dvema metil grupama bočnog niza šest prethodno većsintetisanih β-hidroksi-β-arilalkanskih kiselina koje su derivati β-hidroksi-β-bifenilbuterne kiseline ili β-hidroksi-β,β-difenilpropionske kiseline na inhibiciju enzimaciklooksigenaze kao i na selektivnost prema izoformi ciklooksigenaza-2. Dokingstudijama je ispitan uticaj različitih supstituenata (nitro, trifluorometil, metil, metoksi,dimetilamino grupe i hlora) na benzenovom prstenu sedam derivata 3-hidroksi-3,3-difenilpropanske kiseline na inhibiciju i selektivnost prema COX-2 izoformi. Izračunatesu molekulske zapremine za sva dokovana jedinjenja i utvrđeno je da ispunjavaju uslovda su za minimalno 15 Å3 veće od molekulske zapremine ibuprofena, što znači da suove kiseline potencijalno selektivne za COX-2.Modifikovanom Reformatski reakcijom sintetisano je sedam derivata 3-hidroksi-3,3-difenilpropanske kiseline. Tri planirana jedinjenja nije bilo moguće sintetisati naovaj način, kao ni korišćenjem indijuma kao katalizatora, niti klasičnom Reformatskireakcijom. Modifikovana Reformatski reakcija se sastoji iz dve faze. U prvoj fazi sesintetišu α-bromo alkil 1-etoksiestri iz α-bromsirćetne kiseline i etilvinil etra...
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Dizajniranje, sinteza, fizičko-hemijske i biološke karakteristike ß-hidroksi-ß-arilalkanskih kiselina
UR  - https://hdl.handle.net/21.15107/rcub_nardus_8783
ER  - 

@phdthesis{
author = "Savić, Jelena",
year = "2017",
abstract = "Nesteroidni antiinflamatorni lekovi (NSAIL) se koriste za ublažavanje simptomaakutne i hronične inflamacije već više od pedeset godina. Grupa NSAIL je veomabrojna i obuhvata različite hemijske strukture. Potreba za pronalaženjem novih NSAIL idalje postoji jer neselektivni NSAIL često izazivaju neželjene gastrointestinalne efekte,a neki noviji selektivni lekovi se dovode u vezu sa ozbiljnim neželjenimkardiovaskularnim efektima.U ovoj disertaciji opisani su dizajniranje, sinteza, ispitivanje fizičko-hemijskih ibioloških osobina β-hidroksi-β-arilalkanskih kiselina. U doking studijama je ispitanuticaj α supstitucije jednom ili dvema metil grupama bočnog niza šest prethodno većsintetisanih β-hidroksi-β-arilalkanskih kiselina koje su derivati β-hidroksi-β-bifenilbuterne kiseline ili β-hidroksi-β,β-difenilpropionske kiseline na inhibiciju enzimaciklooksigenaze kao i na selektivnost prema izoformi ciklooksigenaza-2. Dokingstudijama je ispitan uticaj različitih supstituenata (nitro, trifluorometil, metil, metoksi,dimetilamino grupe i hlora) na benzenovom prstenu sedam derivata 3-hidroksi-3,3-difenilpropanske kiseline na inhibiciju i selektivnost prema COX-2 izoformi. Izračunatesu molekulske zapremine za sva dokovana jedinjenja i utvrđeno je da ispunjavaju uslovda su za minimalno 15 Å3 veće od molekulske zapremine ibuprofena, što znači da suove kiseline potencijalno selektivne za COX-2.Modifikovanom Reformatski reakcijom sintetisano je sedam derivata 3-hidroksi-3,3-difenilpropanske kiseline. Tri planirana jedinjenja nije bilo moguće sintetisati naovaj način, kao ni korišćenjem indijuma kao katalizatora, niti klasičnom Reformatskireakcijom. Modifikovana Reformatski reakcija se sastoji iz dve faze. U prvoj fazi sesintetišu α-bromo alkil 1-etoksiestri iz α-bromsirćetne kiseline i etilvinil etra...",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Dizajniranje, sinteza, fizičko-hemijske i biološke karakteristike ß-hidroksi-ß-arilalkanskih kiselina",
url = "https://hdl.handle.net/21.15107/rcub_nardus_8783"
}

Savić, J.. (2017). Dizajniranje, sinteza, fizičko-hemijske i biološke karakteristike ß-hidroksi-ß-arilalkanskih kiselina. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_8783

Savić J. Dizajniranje, sinteza, fizičko-hemijske i biološke karakteristike ß-hidroksi-ß-arilalkanskih kiselina. in Универзитет у Београду. 2017;.
https://hdl.handle.net/21.15107/rcub_nardus_8783 .

Savić, Jelena, "Dizajniranje, sinteza, fizičko-hemijske i biološke karakteristike ß-hidroksi-ß-arilalkanskih kiselina" in Универзитет у Београду (2017),
https://hdl.handle.net/21.15107/rcub_nardus_8783 .

TY  - JOUR
AU  - Savić, Jelena
AU  - Dobričić, Vladimir
AU  - Nikolić, Katarina
AU  - Vladimirov, Sote
AU  - Dilber, Sanda
AU  - Brborić, Jasmina
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2923
AB  - Prediction of gastrointestinal absorption of thirteen newly synthesized beta-hydroxy-beta-arylalkanoic acids (HAA) and ibuprofen was performed using PAMPA test The highest values of PAMPA parameters (%Tand P-app) were calculated for 1C, 1B and 2C and these parameters were significantly lower in comparison to ibuprofen. QSPR analysis was performed in order to identify molecular descriptors with the highest influence on %Tand-logP(app) and to create models which could be used for the design of novel HAA with improved gastrointestinal absorption. Obtained results indicate that introduction of branched side chain, as well as introduction of substituents on one phenyl ring (which disturb symmetry of the molecule) could have positive impact on gastrointestinal absorption. On the basis of these results, six novel HAA were designed and PAMPA parameters %Tand-logP(app) were predicted by use of selected QSPR models. Designed derivatives should have better gastrointestinal absorption than HAA tested in this study.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - In vitro prediction of gastrointestinal absorption of novel beta-hydroxy-beta-arylalkanoic acids using PAMPA technique
VL  - 100
SP  - 36
EP  - 41
DO  - 10.1016/j.ejps.2017.01.005
ER  - 

@article{
author = "Savić, Jelena and Dobričić, Vladimir and Nikolić, Katarina and Vladimirov, Sote and Dilber, Sanda and Brborić, Jasmina",
year = "2017",
abstract = "Prediction of gastrointestinal absorption of thirteen newly synthesized beta-hydroxy-beta-arylalkanoic acids (HAA) and ibuprofen was performed using PAMPA test The highest values of PAMPA parameters (%Tand P-app) were calculated for 1C, 1B and 2C and these parameters were significantly lower in comparison to ibuprofen. QSPR analysis was performed in order to identify molecular descriptors with the highest influence on %Tand-logP(app) and to create models which could be used for the design of novel HAA with improved gastrointestinal absorption. Obtained results indicate that introduction of branched side chain, as well as introduction of substituents on one phenyl ring (which disturb symmetry of the molecule) could have positive impact on gastrointestinal absorption. On the basis of these results, six novel HAA were designed and PAMPA parameters %Tand-logP(app) were predicted by use of selected QSPR models. Designed derivatives should have better gastrointestinal absorption than HAA tested in this study.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "In vitro prediction of gastrointestinal absorption of novel beta-hydroxy-beta-arylalkanoic acids using PAMPA technique",
volume = "100",
pages = "36-41",
doi = "10.1016/j.ejps.2017.01.005"
}

Savić, J., Dobričić, V., Nikolić, K., Vladimirov, S., Dilber, S.,& Brborić, J.. (2017). In vitro prediction of gastrointestinal absorption of novel beta-hydroxy-beta-arylalkanoic acids using PAMPA technique. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 100, 36-41.
https://doi.org/10.1016/j.ejps.2017.01.005

Savić J, Dobričić V, Nikolić K, Vladimirov S, Dilber S, Brborić J. In vitro prediction of gastrointestinal absorption of novel beta-hydroxy-beta-arylalkanoic acids using PAMPA technique. in European Journal of Pharmaceutical Sciences. 2017;100:36-41.
doi:10.1016/j.ejps.2017.01.005 .

Savić, Jelena, Dobričić, Vladimir, Nikolić, Katarina, Vladimirov, Sote, Dilber, Sanda, Brborić, Jasmina, "In vitro prediction of gastrointestinal absorption of novel beta-hydroxy-beta-arylalkanoic acids using PAMPA technique" in European Journal of Pharmaceutical Sciences, 100 (2017):36-41,
https://doi.org/10.1016/j.ejps.2017.01.005 . .

TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Savić, Jelena
AU  - Nikolić, Katarina
AU  - Vladimirov, Sote
AU  - Vujić, Zorica
AU  - Brborić, Jasmina
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2913
AB  - Gastrointestinal absorption of thirteen novel beta-hydroxy-beta-arylalkanoic acids (HAA) with anti-inflammatory activity was predicted by use of biopartitioning micellar chromatography and compared to ibuprofen. All tested HAA have lower retention factors (k) and lower expected gastrointestinal absorption than ibuprofen, whereas derivatives with the highest values of k are 1C, 2APTF and 2C. Quantitative structure-retention relationship (QSRR) analysis was performed in order to identify molecular descriptors with the highest influence on k and ANN(k) model was selected as optimal. Descriptors which form this model (nBM, P VSA_LogP_8 and Eta_L) indicate that replacement of phenyl ring with a saturated or partially unsaturated one, as well as presence of halogens and nitro group should positively affect k values. On the basis of these conclusions, six novel HAA were designed and selected QSRR model was used for the prediction of their k values.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel beta-hydroxy-beta-arylalkanoic acids
VL  - 100
SP  - 280
EP  - 284
DO  - 10.1016/j.ejps.2017.01.023
ER  - 

@article{
author = "Dobričić, Vladimir and Savić, Jelena and Nikolić, Katarina and Vladimirov, Sote and Vujić, Zorica and Brborić, Jasmina",
year = "2017",
abstract = "Gastrointestinal absorption of thirteen novel beta-hydroxy-beta-arylalkanoic acids (HAA) with anti-inflammatory activity was predicted by use of biopartitioning micellar chromatography and compared to ibuprofen. All tested HAA have lower retention factors (k) and lower expected gastrointestinal absorption than ibuprofen, whereas derivatives with the highest values of k are 1C, 2APTF and 2C. Quantitative structure-retention relationship (QSRR) analysis was performed in order to identify molecular descriptors with the highest influence on k and ANN(k) model was selected as optimal. Descriptors which form this model (nBM, P VSA_LogP_8 and Eta_L) indicate that replacement of phenyl ring with a saturated or partially unsaturated one, as well as presence of halogens and nitro group should positively affect k values. On the basis of these conclusions, six novel HAA were designed and selected QSRR model was used for the prediction of their k values.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel beta-hydroxy-beta-arylalkanoic acids",
volume = "100",
pages = "280-284",
doi = "10.1016/j.ejps.2017.01.023"
}

Dobričić, V., Savić, J., Nikolić, K., Vladimirov, S., Vujić, Z.,& Brborić, J.. (2017). Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel beta-hydroxy-beta-arylalkanoic acids. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 100, 280-284.
https://doi.org/10.1016/j.ejps.2017.01.023

Dobričić V, Savić J, Nikolić K, Vladimirov S, Vujić Z, Brborić J. Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel beta-hydroxy-beta-arylalkanoic acids. in European Journal of Pharmaceutical Sciences. 2017;100:280-284.
doi:10.1016/j.ejps.2017.01.023 .

Dobričić, Vladimir, Savić, Jelena, Nikolić, Katarina, Vladimirov, Sote, Vujić, Zorica, Brborić, Jasmina, "Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel beta-hydroxy-beta-arylalkanoic acids" in European Journal of Pharmaceutical Sciences, 100 (2017):280-284,
https://doi.org/10.1016/j.ejps.2017.01.023 . .

TY  - JOUR
AU  - Savić, Jelena
AU  - Dilber, Sanda
AU  - Milenković, Marina
AU  - Kotur-Stevuljević, Jelena
AU  - Marković, Bojan
AU  - Vladimirov, Sote
AU  - Brborić, Jasmina
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2891
AB  - Background: Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects. Methods: Eight beta-hydroxy-beta-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats. Results: Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen. Conclusion: The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Medicinal Chemistry
T1  - Docking Studies, Synthesis and Biological Evaluation of beta-aryl-beta-hydroxy Propanoic Acids for Anti-inflammatory Activity
VL  - 13
IS  - 2
SP  - 186
EP  - 195
DO  - 10.2174/1573406412666160907150247
ER  - 

@article{
author = "Savić, Jelena and Dilber, Sanda and Milenković, Marina and Kotur-Stevuljević, Jelena and Marković, Bojan and Vladimirov, Sote and Brborić, Jasmina",
year = "2017",
abstract = "Background: Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects. Methods: Eight beta-hydroxy-beta-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats. Results: Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen. Conclusion: The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Medicinal Chemistry",
title = "Docking Studies, Synthesis and Biological Evaluation of beta-aryl-beta-hydroxy Propanoic Acids for Anti-inflammatory Activity",
volume = "13",
number = "2",
pages = "186-195",
doi = "10.2174/1573406412666160907150247"
}

Savić, J., Dilber, S., Milenković, M., Kotur-Stevuljević, J., Marković, B., Vladimirov, S.,& Brborić, J.. (2017). Docking Studies, Synthesis and Biological Evaluation of beta-aryl-beta-hydroxy Propanoic Acids for Anti-inflammatory Activity. in Medicinal Chemistry
Bentham Science Publ Ltd, Sharjah., 13(2), 186-195.
https://doi.org/10.2174/1573406412666160907150247

Savić J, Dilber S, Milenković M, Kotur-Stevuljević J, Marković B, Vladimirov S, Brborić J. Docking Studies, Synthesis and Biological Evaluation of beta-aryl-beta-hydroxy Propanoic Acids for Anti-inflammatory Activity. in Medicinal Chemistry. 2017;13(2):186-195.
doi:10.2174/1573406412666160907150247 .

Savić, Jelena, Dilber, Sanda, Milenković, Marina, Kotur-Stevuljević, Jelena, Marković, Bojan, Vladimirov, Sote, Brborić, Jasmina, "Docking Studies, Synthesis and Biological Evaluation of beta-aryl-beta-hydroxy Propanoic Acids for Anti-inflammatory Activity" in Medicinal Chemistry, 13, no. 2 (2017):186-195,
https://doi.org/10.2174/1573406412666160907150247 . .

TY  - CONF
AU  - Savić, Jelena
AU  - Brborić, Jasmina
AU  - Dilber, Sanda
AU  - Vladimirov, Sote
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5362
AB  - Although non-steroidal anti-inflammatory agents (NSAID) are numerous, broad used and can be procured as OTC drugs, search for new non-steroidal NSAID is continuing. Main motive is to find compound which selectively inhibits inducible form of enzyme cyclooxygenase (COX-2), but would have at least 10 times less effect on constitutive form (COX-1). If this selectivity concept is achieved, adverse effect on gastric mucosa would be avoided [1]. According to current docking studies, a compound is considered selective if it can maintain interactions in hydrophilic side pocket, so called P3 region in the active site of COX-2 [2]. The aim of this study was to determine the impact of substitution of one or both phenyl rings in 3-hydroxy-3,3-diphenylpropanoic acid with some simple substituents on selectivity towards COX-2 inhibition. Molecular docking calculations were performed using Autodock v4.0.1 into the 3D structure of the catalytic site of COX-2 enzyme (pdb code: 1cx2). Structure of each compound was generated using the ChemOffice v7.0 Ultra software package and have been MM2 optimized. Each docking experiment consisted of 100 docking runs with 150 individuals and 500,000 energy evaluations. The structures were incorporated into 40x40x40 grid points receptor pocket, which was centered to the position of ibuprofen in crystallographic structure of the complex. Ibuprofen was used as a reference compound because of its structure similarity to tested compounds. All of the compounds have lower binding energies than ibuprofen (Fig. 1) and all of these compounds have the right structure which enables penetration into P3 region in the COX-2. Compound containing dimethylamino group penetrates deepest into this region indicating the best selectivity ratio of all tested compounds.
PB  - Serbian Chemical Society
C3  - ICOSECS 8, 8th International Conference of the Chemical Societies of the South-East European Countries, BOOK OF ABSTRACTS, Belgrade, Serbia, June 27-29
T1  - Docking studies of 3-hydroxy-3-arylpropionic acids as potentially selective COX-2 inhibitors
SP  - 101
EP  - 101
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5362
ER  - 

@conference{
author = "Savić, Jelena and Brborić, Jasmina and Dilber, Sanda and Vladimirov, Sote",
year = "2013",
abstract = "Although non-steroidal anti-inflammatory agents (NSAID) are numerous, broad used and can be procured as OTC drugs, search for new non-steroidal NSAID is continuing. Main motive is to find compound which selectively inhibits inducible form of enzyme cyclooxygenase (COX-2), but would have at least 10 times less effect on constitutive form (COX-1). If this selectivity concept is achieved, adverse effect on gastric mucosa would be avoided [1]. According to current docking studies, a compound is considered selective if it can maintain interactions in hydrophilic side pocket, so called P3 region in the active site of COX-2 [2]. The aim of this study was to determine the impact of substitution of one or both phenyl rings in 3-hydroxy-3,3-diphenylpropanoic acid with some simple substituents on selectivity towards COX-2 inhibition. Molecular docking calculations were performed using Autodock v4.0.1 into the 3D structure of the catalytic site of COX-2 enzyme (pdb code: 1cx2). Structure of each compound was generated using the ChemOffice v7.0 Ultra software package and have been MM2 optimized. Each docking experiment consisted of 100 docking runs with 150 individuals and 500,000 energy evaluations. The structures were incorporated into 40x40x40 grid points receptor pocket, which was centered to the position of ibuprofen in crystallographic structure of the complex. Ibuprofen was used as a reference compound because of its structure similarity to tested compounds. All of the compounds have lower binding energies than ibuprofen (Fig. 1) and all of these compounds have the right structure which enables penetration into P3 region in the COX-2. Compound containing dimethylamino group penetrates deepest into this region indicating the best selectivity ratio of all tested compounds.",
publisher = "Serbian Chemical Society",
journal = "ICOSECS 8, 8th International Conference of the Chemical Societies of the South-East European Countries, BOOK OF ABSTRACTS, Belgrade, Serbia, June 27-29",
title = "Docking studies of 3-hydroxy-3-arylpropionic acids as potentially selective COX-2 inhibitors",
pages = "101-101",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5362"
}

Savić, J., Brborić, J., Dilber, S.,& Vladimirov, S.. (2013). Docking studies of 3-hydroxy-3-arylpropionic acids as potentially selective COX-2 inhibitors. in ICOSECS 8, 8th International Conference of the Chemical Societies of the South-East European Countries, BOOK OF ABSTRACTS, Belgrade, Serbia, June 27-29
Serbian Chemical Society., 101-101.
https://hdl.handle.net/21.15107/rcub_farfar_5362

Savić J, Brborić J, Dilber S, Vladimirov S. Docking studies of 3-hydroxy-3-arylpropionic acids as potentially selective COX-2 inhibitors. in ICOSECS 8, 8th International Conference of the Chemical Societies of the South-East European Countries, BOOK OF ABSTRACTS, Belgrade, Serbia, June 27-29. 2013;:101-101.
https://hdl.handle.net/21.15107/rcub_farfar_5362 .

Savić, Jelena, Brborić, Jasmina, Dilber, Sanda, Vladimirov, Sote, "Docking studies of 3-hydroxy-3-arylpropionic acids as potentially selective COX-2 inhibitors" in ICOSECS 8, 8th International Conference of the Chemical Societies of the South-East European Countries, BOOK OF ABSTRACTS, Belgrade, Serbia, June 27-29 (2013):101-101,
https://hdl.handle.net/21.15107/rcub_farfar_5362 .

TY  - JOUR
AU  - Savić, Jelena
AU  - Dilber, Sanda
AU  - Marković, Bojan
AU  - Milenković, Marina
AU  - Vladimirov, Sote
AU  - Juranić, Ivan O.
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1483
AB  - Six beta-hydroxy-beta-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl propanoic acids, and to elucidate the effect a-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carragenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED(50) values is between 127 mu mol/kg and 15 mu mol/kg, while the result for ibuprofen is 51.7 mu mol/kg. Only slight hyperaemia or few petechiae were spotted on rat's stomach. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenylpropanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions.
PB  - MDPI, Basel
T2  - Molecules
T1  - Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids
VL  - 16
IS  - 8
SP  - 6645
EP  - 6655
DO  - 10.3390/molecules16086645
ER  - 

@article{
author = "Savić, Jelena and Dilber, Sanda and Marković, Bojan and Milenković, Marina and Vladimirov, Sote and Juranić, Ivan O.",
year = "2011",
abstract = "Six beta-hydroxy-beta-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl propanoic acids, and to elucidate the effect a-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carragenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED(50) values is between 127 mu mol/kg and 15 mu mol/kg, while the result for ibuprofen is 51.7 mu mol/kg. Only slight hyperaemia or few petechiae were spotted on rat's stomach. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenylpropanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids",
volume = "16",
number = "8",
pages = "6645-6655",
doi = "10.3390/molecules16086645"
}

Savić, J., Dilber, S., Marković, B., Milenković, M., Vladimirov, S.,& Juranić, I. O.. (2011). Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids. in Molecules
MDPI, Basel., 16(8), 6645-6655.
https://doi.org/10.3390/molecules16086645

Savić J, Dilber S, Marković B, Milenković M, Vladimirov S, Juranić IO. Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids. in Molecules. 2011;16(8):6645-6655.
doi:10.3390/molecules16086645 .

Savić, Jelena, Dilber, Sanda, Marković, Bojan, Milenković, Marina, Vladimirov, Sote, Juranić, Ivan O., "Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids" in Molecules, 16, no. 8 (2011):6645-6655,
https://doi.org/10.3390/molecules16086645 . .