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 . .