Design, Synthesis And Evaluation Of Cox Inhibitory Activity And Antiproliferative Effects Of Novel Ibuprofen/1,2,4-Triazole Hybrids

Balaban Özdoğan A., Avcı A., Sağlık Özkan B. N., Karaduman A. B., Gökhan Kelekçi N., Tozkoparan Köprücü B.

VIII. Ulusal I. Uluslararası Katılımlı Farmasötik Kimya Kongresi, Kayseri, Türkiye, 29 - 31 Ekim 2026, ss.1-2, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Kayseri
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.1-2
  • Hacettepe Üniversitesi Adresli: Evet

Özet

Growing evidence highlights the close relationship between chronic inflammation and cancer, with COX-2 playing an important role in tumor proliferation, angiogenesis, resistance to apoptosis, and inflammatory responses. Given the well-established antiinflammatory and anticancer activities of 1,2,4-triazole and acetamide pharmacophores, multifunctional molecules targeting both inflammatory and oncogenic pathways represent a promising drug discovery strategy [1-5]. Based on this rationale, novel ibuprofen-1,2,4-triazole-acetamide hybrids were designed through molecular hybridization to combine these pharmacologically relevant structural features within a single molecular framework and were evaluated for their COX inhibitory and antiproliferative activities. Accordingly, 26 novel 2-[(3-(1-(4-isobutylphenyl)ethyl)-1,2,4-triazol-5-yl)thio]-N-(substituted phenyl)acetamide derivatives were synthesized and characterized using IR, 1H-NMR, 13C-NMR, HSQC, and HRMS. Their cyclooxygenase inhibitory activities were evaluated in vitro and compared with 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) exhibited remarkable COX-2 inhibitory activity [6]. Compounds 5a5 and 5a15 also showed strong COX-2 selectivity (selectivity index >100). Antiproliferative activities were evaluated by MTT assay using MCF-7, HT29, HepG2, C6, and NIH3T3 cell lines. Compounds 5a5, 5a15, and 5a26 exhibited cytotoxic activities comparable to doxorubicin in cancer cell lines while showing lower cytotoxicity against healthy NIH3T3 cells [7]. These findings suggest that selective COX-2 inhibitory compounds with significant antiproliferative activity may represent promising dual-acting candidates with both antiinflammatory and anticancer properties.


References


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