Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1367, 2026 (SCI-Expanded, Scopus)
Benzimidazolium–chalcone salts were synthesized and structurally characterized by FT-IR, 1H & 13C NMR, and HR-MS. Their acetylcholinesterase (AChE) inhibitory, anticancer, and antibacterial activities were systematically evaluated. Several compounds exhibited potent AChE inhibition, with compound 3a showing the strongest activity. Anticancer efficacy was assessed against A549 human lung adenocarcinoma cells, where the most active compound displayed an IC₅₀ value of 3.74 ± 0.15 µM, while showing no significant cytotoxicity toward NIH/3T3 normal fibroblasts. Mechanistic studies revealed the induction of late-stage apoptosis in A549 cells. Selected compounds also demonstrated strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations of 2 µg/mL. Despite identical MIC values, the compounds differentially modulated mepA gene expression, a resistance-associated MATE efflux pump gene in MRSA. Quantitative real-time PCR analysis revealed a significant, dose-dependent upregulation of mepA expression (p < 0.001), indicating bacterial stress responses and suggesting distinct antibacterial mechanisms beyond growth inhibition. Notably, compound 3a exhibited pronounced antibiofilm activity (77.1 ± 0.49% inhibition at 2 × MIC). Molecular docking studies supported the experimental data, showing that compound 3a had the highest binding affinity toward AChE (PDB ID: 4EY7; −9.631 kcal/mol). Overall, these results identify benzimidazolium–chalcone salts as promising multifunctional candidates with AChE inhibitory, anticancer, and anti-MRSA potential, supported by mechanistic gene expression insights.