Synthesis, In Vitro Evaluation, and Molecular Docking Studies of Novel 3,5-Diphenyl-1<i>H</i>-1,2,4-Triazole Derivatives as Potential hEGFR Inhibitors

KOLCUOĞLU Y., BEKİRCAN O., Ustalar N., TÜRE A., Akdemir A., Sanlier S. H.

ARCHIV DER PHARMAZIE, cilt.358, sa.5, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 358 Sayı: 5
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/ardp.70007
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
  • Anahtar Kelimeler: 3,5-diphenyl-1H-1,2,4-triazole, docking, hEGFR, molecular modeling, semicarbazide, thiosemicarbazides
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

EGFR, an important target in cancer chemotherapy, is an important component of the signaling system that regulates important cellular processes such as growth, differentiation, metabolism, and apoptosis in response to both internal and external stimuli. Based on this approach, comprehensive modeling studies targeting the EGFR protein were performed, and synthesized molecules were proposed. For this purpose, the synthesis of new 3,5-diphenyl-1H-1,2,4-triazole derivatives containing semicarbazide, thiosemicarbazide, 1,2,4-triazole-3-thione, and 1,2,4-triazole-3-one units was carried out. Among these compounds, 6a-6i presented in the present study exhibited EGFR inhibition in the nanomolar range. In addition, molecules 5e and 6e showed significant IC50 values. Compound 6e showed the closest IC50 value to gefitinib, a well-known EGFR inhibitor, with its noncompetitive inhibition mode. The Ki value of compound 6e was determined as 0.174 mu M.