Imidazole-based hydrazones as potent anti-colon cancer agents: Design, synthesis, biological evaluation and computational studies

Tapera M., Doğan E., Şahin K., Gözkamane G. A., Kekeçmuhammed H., Sandal S., ...Daha Fazla

Journal of Molecular Structure, cilt.1318, 2024 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1318
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.molstruc.2024.139240
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: Anticancer, Hydrazone, Imidazole, Molecular docking, Synthesis
  • Erciyes Üniversitesi Adresli: Evet

Özet

Compounds containing imidazole and hydrazone structural frameworks have been widely studied and demonstrated to exhibit a wide range of pharmacological properties. In this study, a descriptive series of 20 new hybrid compounds composed of an imidazole ring and a hydrazone moiety were designed and synthesized through multistep chemical reactions. Synthesized compounds were characterized by various spectral techniques, including FT-IR, 1H NMR, 13C NMR and HRMS. Furthermore, the proposed structure of AB-1 was resolved by single-crystal X-ray analysis. The compounds were evaluated for their in vitro anti-colon cancer activity, and the most promising compounds (i.e., AB-6, AB-9, AB-11 and AB-18) exhibited significant dose- and time-dependent cytotoxicity with selectivity to HT-29 and HCT-116 cells. In addition, Molecular docking, molecular dynamics simulations, and binding free energy analyses were carried out to better understand the structure-activity relationships and mechanisms of action of the potential anticancer agents. Our preliminary findings suggest that compounds AB-6, AB-9, AB-11, and AB-18 could be exploited as a leading structure for further anticancer drug development.