Multifunctional benzimidazolium derivatives as anticancer, antibacterial, and acetylcholinesterase inhibitors: In vitro and molecular docking studies

Abstract

In this study, a series of benzimidazolium derivatives were synthesized and characterized using HR-MS, FTIR, ¹H NMR, and ¹³C NMR techniques. Their acetylcholinesterase (AChE) inhibitory potentials, anticancer activities against MCF-7 breast cancer cells, and antibacterial effects against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, as well as resistant strains such as MRSA and MDR Escherichia coli were experimentally evaluated. Additionally, their antibiofilm activities against MRSA and MDR E. coli were also assessed. These experimental findings were further supported by molecular docking studies. Among the tested compounds, compound 6c exhibited the highest AChE inhibitory activity, with an IC₅₀ value of 9.32 μM. It also demonstrated the most potent anticancer activity against MCF-7 cells, with an IC₅₀ value of 1.8 μM. All synthesized compounds exhibited antibacterial activity against both drug-resistant and non-resistant bacterial strains. Furthermore, compound 6c showed the strongest molecular docking interactions with AChE and MRSA-associated proteins, with binding energy scores of −9.386 kcal/mol (4EY7), −8.180 kcal/mol (1 ZGC), and −6.301 kcal/mol (3ZG5), respectively. This is the first report integrating AChE inhibition, anticancer, antibacterial, and antibiofilm evaluations of novel benzimidazolium derivatives in combination with molecular docking, thereby providing a multi-targeted framework for the development of new therapeutic agents against neurodegenerative diseases, cancer, and multidrug-resistant infections.