Exploration of Remarkably Potential Multitarget-Directed N-Alkylated-2-(substituted phenyl)-1H-benzimidazole Derivatives as Antiproliferative, Antifungal, and Antibacterial Agents

Improving lipophilicity for drugs to penetrate the lipidmembraneand decreasing bacterial and fungal coinfections for patients withcancer pose challenges in the drug development process. Here, a seriesof new N-alkylated-2-(substituted phenyl)-1H-benzimidazolederivatives were synthesized and characterized by H-1 and C-13 NMR, FTIR, and HRMS spectrum analyses to address thesedifficulties. All the compounds were evaluated for their antiproliferative,antibacterial, and antifungal activities. Results indicated that compound 2g exhibited the best antiproliferative activity against theMDA-MB-231 cell line and also displayed significant inhibition atminimal inhibitory concentration (MIC) values of 8, 4, and 4 & mu;gmL(-1) against Streptococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus compared with amikacin. The antifungaldata of compounds 1b, 1c, 2e, and 2g revealed their moderate activities toward Candida albicans and Aspergillus niger,with MIC values of 64 & mu;g mL(-1) for both strains.Finally, the molecular docking study found that 2g interactedwith crucial amino acids in the binding site of complex dihydrofolatereductase with nicotinamide adenine dinucleotide phosphate.