Structure-based design of functionalized 2-substituted and 1,2- disubstituted benzimidazole derivatives and their in vitro antibacterial efficacy

Abstract The aim of this present study was to synthesize 2-substituted and 1,2-disubstituted benzimidazole derivatives to investigate their antibacterial diversity for possible future drug design. The structure-based design of precursors 2-(1H-benzimidazol-2-yl)aniline 1 , 2-(3,5-dinitro phenyl)-1H-benzimidazole 3 and 2-benzyl-1H-benzimidazole 5 were achieved by the condensation reaction of o -phenylenediamine with anthranilic acid, 3,5-dinitrophenylbenzoic acid, and phenylacetic acid, respectively. The precursors 1 , 3 and 5 , upon reaction with six different electrophile-releasing agents, furnished the corresponding 2-substituted benzimidazole, 2a-f and 1,2-disubstituted benzimidazole derivatives 4a-f and 6a-f , respectively. The structural identity of the targeted compounds was authenticated by elemental analytical data and spectral information from FT-IR, UV, 1 H, and 13 C NMR. The outcome of the findings from the in vitro screening unveiled 2-benzyl-1-(phenylsulfonyl)-1H-benzimidazole 6b as the most active derivative with lowest MIC value of 15.63 µg/mL.