Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site
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'...
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| Format: | Article |
| Language: | srp |
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Pharmaceutical Association of Serbia, Belgrade, Serbia
2023-01-01
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| Series: | Arhiv za farmaciju |
| Subjects: | |
| Online Access: | https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2023/0004-19632303205S.pdf |
| _version_ | 1797743704173182976 |
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| author | Savić Jelena Antonijević Marija Crevar Milkica Brborić Jasmina |
| author_facet | Savić Jelena Antonijević Marija Crevar Milkica Brborić Jasmina |
| author_sort | Savić Jelena |
| collection | DOAJ |
| description | 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 b-hydroxy-b-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 b-hydroxy-b-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. |
| first_indexed | 2024-03-12T14:59:15Z |
| format | Article |
| id | doaj.art-2a8c6fc644604cddb9767a88fd31547b |
| institution | Directory Open Access Journal |
| issn | 0004-1963 2217-8767 |
| language | srp |
| last_indexed | 2024-03-12T14:59:15Z |
| publishDate | 2023-01-01 |
| publisher | Pharmaceutical Association of Serbia, Belgrade, Serbia |
| record_format | Article |
| series | Arhiv za farmaciju |
| spelling | doaj.art-2a8c6fc644604cddb9767a88fd31547b2023-08-14T09:07:41ZsrpPharmaceutical Association of Serbia, Belgrade, SerbiaArhiv za farmaciju0004-19632217-87672023-01-017332052150004-19632303205SDocking studies of some pyrazole containing compounds in the cyclooxygenase-2 active siteSavić Jelena0https://orcid.org/0000-0002-8508-5538Antonijević Marija1Crevar Milkica2https://orcid.org/0000-0002-6947-4824Brborić Jasmina3https://orcid.org/0000-0002-5202-8334University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Beograd, SerbiaHemofarm a.d, Vršac, SerbiaUniversity of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Beograd, SerbiaUniversity of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Beograd, SerbiaWhereas 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 b-hydroxy-b-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 b-hydroxy-b-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.https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2023/0004-19632303205S.pdfcyclooxygenase-2 inhibitorsmolecular interactionsrational drug designprotein-ligand interactionsb-hydroxy-b-arylpropanoic acids |
| spellingShingle | Savić Jelena Antonijević Marija Crevar Milkica Brborić Jasmina Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site Arhiv za farmaciju cyclooxygenase-2 inhibitors molecular interactions rational drug design protein-ligand interactions b-hydroxy-b-arylpropanoic acids |
| title | Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site |
| title_full | Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site |
| title_fullStr | Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site |
| title_full_unstemmed | Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site |
| title_short | Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site |
| title_sort | docking studies of some pyrazole containing compounds in the cyclooxygenase 2 active site |
| topic | cyclooxygenase-2 inhibitors molecular interactions rational drug design protein-ligand interactions b-hydroxy-b-arylpropanoic acids |
| url | https://scindeks-clanci.ceon.rs/data/pdf/0004-1963/2023/0004-19632303205S.pdf |
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