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

In this study, a series of derivatives of pyrazole hybrid structurescontaining carbonitrile and substituted thiazole moiety weredesigned to search for selective COX-2 inhibition. The designedtarget structures were synthesized with easy, practical, andefficient procedures. COX-1/2 inhibition and cytotoxic effects ofthe synthesized compounds were evaluated in NIH/3T3 andMDA-MD-231 cell lines for inhibition concentration and selectiv-ity index. The results showed that the compounds have aninhibitory effect with higher selectivity towards COX-2 overall inboth cell lines and moderate antiproliferative activity bytargeting the breast cancer cell line MDA-MB-231. Among the19 compounds synthesized (19 a–t), especially compound 19 mwas found to be highly effective with COX-2 inhibition of5.63 μM in the NIH/3T3 cell line and 4.12 μM in the MDA-MB-231 cell line. Moreover, molecular docking studies showed thatthe compounds indeed exhibited higher affinity for the COX-2active site. The theoretical ADMET properties of the presentedcompounds were calculated, and the results showed that thecompounds may have a more favorable pharmacokinetic effectprofile than the selective COX-2 inhibitor Celecoxib, thuspromising COX-2 inhibitor drug candidates for the future.