YENİ İBUPROFEN/1,2,4-TRİAZOL HİBRİTLERİNİN TASARIMI, SENTEZİ VE COX İNHİBİTÖR AKTİVİTE İLE ANTİPROLİFERATİF ETKİLERİNİN DEĞERLENDİRİLMESİ

Abstract

In this study, a total of 26 novel hybrid compounds with the structure of 2-[(3-(1-(4-isobutylphenyl)ethyl)-1,2,4-triazol-5-yl)thio]-N-(substituted phenyl)acetamide were synthesized using the molecular hybridization approach. The melting points of the target compounds were determined, and their structures were elucidated using IR, 1H-NMR, 13C-NMR, HSQC, and HRMS spectral analysis techniques. The cyclooxygenase enzyme inhibition activities of the compounds were evaluated in vitro, and the results were compared with those of the reference compounds ibuprofen (COX-2/IC50 = 5,326 ± 0,218 μM), celecoxib (COX-2/IC50 = 0,132 ± 0,005 μM) and nimesulide (COX-2/IC50 = 1,684 ± 0,079 μM). Compounds 5a5 (2-NO2, IC50 = 1,921 ± 0,086 μM), 5a14 (4-OCH3, IC50 = 0,240 ± 0,010 μM), 5a15 (4-Cl, IC50 = 2,881 ± 0,136 μM), 5a16 (4-NO2, IC50 = 0,169 ± 0,007 μM) and 5a26 (2,5-OCH3-4-NO2, IC50 = 0,326 ± 0,014 μM) were found to exhibit remarkable COX-2 inhibitory activity. In addition, compounds 5a5 (selectivity index >100) and 5a15 (selectivity index >100) demonstrated strong selectivity profiles toward the COX-2 enzyme. Furthermore, the antiproliferative activities of the target compounds were evaluated by the MTT assay using MCF-7, HT29, HepG2, C6, and NIH3T3 cell lines. The obtained results revealed that compounds 5a5, 5a15, and 5a26 exhibited cytotoxic activities comparable to doxorubicin in cancer cell lines, while showing lower cytotoxicity against the healthy NIH3T3 cell line. Notably, the significant antiproliferative effects of these selective COX-2 inhibitory compounds against various cancer cell lines suggest that these structures may be considered promising dual-acting candidate molecules possessing both antiinflammatory and anticancer properties.