Facile, One-pot, pseudo four component synthesis of novel benzimidazolyl- thiazoles via multi-component approach and their biological evaluation

Abstract

Abstract A general and sustainable multicomponent approach for the synthesis of benzimidazolyl-thiazole compounds via an efficient, one-pot, pseudo four-component reaction using 5-amino-2-mercaptobenzimidazole, aralkyl halides, ammonium thiocyanate, and substituted α-bromo-acetophenones in glacial acetic acid at ambient temperature to give final compounds (4a-p) in good yields in shorter time. The spectral data of synthesized compounds were evaluated by analytical and spectral techniques (IR, 1H-NMR, 13C-NMR, and ESI-HRMS). Further, some of the synthesized compounds were screened for their in-vitro antibacterial activity studies using the agar well diffusion method against Gram-positive Streptococcus Pneumoniae (2451) bacteria and Gram-negative Porteous Mirabilis (2081) bacteria. Based on the MIC results, it was observed that the most active compounds 4b, 4e, 4f, and 4k are shown promising anti-bacterial activity with the zone of inhibition values of 2.85 cm 2.75 cm, 3.6 cm, and 3.3 cm against both Gram-negative and Gram-positive bacteria cell lines respectively. Further, we have also insight into the molecular simulation studies, based on the binding results, compound 4i showed stable binding interactions with streptomycin drug with active site of the gyrase protein (PDB ID: 1KIJ). The structure-activity relationship (SAR) studies of all the title scaffolds were also established. The antibacterial activity, molecular docking studies, molecular dynamic simulations of the title compounds were suggested that these are promising anti-bacterial active skeletons.