Novel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX-2 Inhibition

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dc.authoridKARAKUŞ, Fuat/0000-0002-5260-3650
dc.authoridKuzu, Burak/0000-0002-7305-7177
dc.contributor.authorArzuk, Ege
dc.contributor.authorKarakus, Fuat
dc.contributor.authorErguc, Ali
dc.contributor.authorKuzu, Burak
dc.date.accessioned2024-08-31T07:50:32Z
dc.date.available2024-08-31T07:50:32Z
dc.date.issued2024
dc.departmentEge Üniversitesien_US
dc.description.abstractIn this study, a series of derivatives of pyrazole hybrid structures containing carbonitrile and substituted thiazole moiety were designed to search for selective COX-2 inhibition. The designed target structures were synthesized with easy, practical, and efficient procedures. COX-1/2 inhibition and cytotoxic effects of the synthesized compounds were evaluated in NIH/3T3 and MDA-MD-231 cell lines for inhibition concentration and selectivity index. The results showed that the compounds have an inhibitory effect with higher selectivity towards COX-2 overall in both cell lines and moderate antiproliferative activity by targeting the breast cancer cell line MDA-MB-231. Among the 19 compounds synthesized (19 a-t), especially compound 19 m was found to be highly effective with COX-2 inhibition of 5.63 mu M in the NIH/3T3 cell line and 4.12 mu M in the MDA-MB-231 cell line. Moreover, molecular docking studies showed that the compounds indeed exhibited higher affinity for the COX-2 active site. The theoretical ADMET properties of the presented compounds were calculated, and the results showed that the compounds may have a more favorable pharmacokinetic effect profile than the selective COX-2 inhibitor Celecoxib, thus promising COX-2 inhibitor drug candidates for the future. A series of derivatives of pyrazole hybrid structures were designed to search for selective COX-2 inhibition. COX-1/2 inhibition and cytotoxic effects of the synthesized compounds were evaluated in NIH/3T3 and MDA-MD-231 cell lines. Moreover, molecular docking, SAR, and ADMET studies showed that the compounds may have a more favorable pharmacokinetic profile, thus promising COX-2 inhibitor drug candidates for the future.imageen_US
dc.description.sponsorshipScientific and Technologic Research Agency of Turkey (TUBITAK) [223S065]en_US
dc.description.sponsorshipThis study was funded by Scientific and Technologic Research Agency of Turkey (TUBITAK) (grant number: 223S065).en_US
dc.identifier.doi10.1002/slct.202304783
dc.identifier.issn2365-6549
dc.identifier.issue1en_US
dc.identifier.scopus2-s2.0-85181214876en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1002/slct.202304783
dc.identifier.urihttps://hdl.handle.net/11454/105277
dc.identifier.volume9en_US
dc.identifier.wosWOS:001134982400001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherWiley-V C H Verlag Gmbhen_US
dc.relation.ispartofChemistryselecten_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240831_Uen_US
dc.subjectThiazolyl-Pyrazoleen_US
dc.subjectCox-2 Inhibitionen_US
dc.subjectMolecular Dockingen_US
dc.subjectAdmeten_US
dc.subjectSaren_US
dc.titleNovel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX-2 Inhibitionen_US
dc.typeArticleen_US

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