Evaluation of anti-cancer and anti-enzyme activities of imidazole derivative molecules with theoretical calculations

Abstract

Nitrogen-containing heterocycles, known for their biological activity, were synthesized as four novel imidazolebased compounds via the reaction of guanyl hydrazones with 2-bromoacetyl naphthalene. The aim of this study was to synthesize and characterize these compounds and evaluate their potential as cholinesterase inhibitors and anticancer agents. Structural elucidation was performed using 1H NMR, 13C NMR, FTIR, and MS. All compounds exhibited strong AChE and BChE inhibitory activities, with Ki values ranging from 131.44 to 415.54 nM (AChE) and 95.74 to 154.62 nM (BChE). IC50 values confirmed potent inhibition. MTT assays demonstrated dose-dependent antiproliferative effects, with greater cytotoxicity observed in A2780 ovarian cancer cells than in MIA PaCa-2 pancreatic cells. In silico studies, including Gaussian (B3LYP, HF, M062X/6-31++G(d,p)), molecular docking, and ADME/T analyses, supported the pharmacological potential of these compounds. These findings highlight their promise as candidates for further development in cholinesterase inhibition and cancer therapy.