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

• Published in: Journal of molecular structure Vol. 1318; p. 139240
• Main Authors: Tapera, Michael, Doğan, Eylül, Şahin, Kader, Gözkamane, Gaye Alara, Kekeçmuhammed, Hüseyin, Sandal, Semiha, Gurkan, Ajda Coker, Bora, Rıfat Emin, Anber, Anber, Durdagi, Serdar, Zorlu, Yunus, Sarıpınar, Emin
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-12-2024
• Subjects: Anticancer; Hydrazone; Imidazole; Molecular docking; Synthesis; Synthesis; Hydrazone; Anticancer; Imidazole; Molecular docking
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139240

•Synthesis of imidazole and hydrazone hybrids as anticancer agents.•The inhibitive effect of synthesized compounds on HCT-116 and HT-29 cell viability.•Computational studies were performed to acquire insights into the binding interactions, identifying local reactivity properties and pharmaceutical stability of the compounds.
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.