Synthesis, characterization, cytotoxic evaluation, and molecular docking studies of novel 1,2,3-triazole-based chalcones for potential anticancer applications

Abstract

Hybrid molecules of pharmacophores could enhance the desired pharmacological activity while minimizing the side effects and drug resistance associated with individual pharmacophores. In this study, we synthesized twelve bis-1,2,3-triazole-based chalcones (78–90 %) yield) in five steps and characterized them via IR, 1H NMR, 13C NMR, and HRMS spectroscopy. Seven hybrid molecules demonstrated good cytotoxicity against A-549 lung cancer cells in the MTT cell viability assay (IC50 = 44.72±0.66 to 86.22±1.06 µM), which is comparable to the IC50 of the anticancer drug doxorubicin (39.86±1.15 µM). Molecular docking studies of the hybrid molecules with extracellular signal-regulated kinase 2/mitogen-activated protein kinase 1 (ERK2) (PDB ID: 4ZXT), which is triggered by lung cancer, showed excellent binding interactions (H-bonding, hydrophobic interactions, halogen bonding, etc.) between the drug candidates and target receptors (binding energy = −7.7 to −9.7 kcal/mol). We believe that these hybrid molecules could have potential applications as anticancer agents.

Keywords

• 1,2,3-triazole
• Chalcones
• Cytotoxicity
• Molecular docking
• Hybrid molecules