Synthesis and effect of N-alkylation on antibacterial activity of 2-(Benzylthio) methyl-1H-benzimidazole derivatives

Abstract

In pursuit the development of novel potent and selective antibacterial agents, we synthesized twelve (12) N-alkyl 2-benzylthiomethyl-1H-benzimidazole derivatives and evaluated their antibacterial activities. Their antibacterial profile was determined with minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) against a small set of two (2) strains Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive). These compounds are produced by the condensation reaction of 2-benzylthiomethyl-1H-benzimidazole (5) with benzyl chloride or bromide (6) in the presence of potassium carbonate (K2CO3). The panel of twelve synthetized compounds (7a-l) were characterized by NMR 1H, 13C spectroscopy, and high-resolution mass spectrometry (HRMS). The results showed that compounds 7a, 7b, 7c, 7d, 7e, 7f, 7h, 7k, and 7l were potent against Escherichia coli and Staphylococcus aureus, with significant MICs values from 140 to 290 µg/mL. On E. coli, five (5) compounds 7b, 7f, 7i, 7k and 7l showed bactericidal effects within common an N-alkylation by R3= phenyl, methyl, and CH2OH on the benzimidazole scaffold and the benzylthiol substituted by R2= Cl or CF3. This is evidence or a probe of these chemical groups implementing the bactericidal activity.