One-pot, three-component synthesis, anti-bacterial and molecular modelling studies of novel benzimidazole based isoindoline-1,3-dione and benzo[4,5]imidazo[2,1-b]thiazol hybrids

Abstract A series of metal-free, thioalkylated benzimidazole-based isoindoline-1,3-dione ( 4a-w) and N -fused 4,5-benzo[4,5]imidaz[2,1- b ]thiazole ( 5a-h) derivatives were synthesized via a novel, one-pot three-component approach. All the synthesized scaffolds were well characterized by analytical and spectroscopic techniques. The usefulness of this reaction is that it involves easy workup, shorter reaction time, broad substrate scope, and column-free purification of the products. Further, the synthesized scaffolds ( 4a-w ) were evaluated for their in-vitro anti-microbial activity using two Gram-positive and two Gram-negative bacterial cell lines Escherichia coli, Salmonella typhi, Staphylococcus aureus and Micrococcus luteus by agar well diffusion method. Among tested compounds, compounds 4a, 4g, 4j, 4q, 4s, and 4t showed significant invitro antibacterial activity against Gram-positive and Gram-negative bacterial cell lines. Further, we have also insight of molecular docking studies, based on the docking results compounds 4s, 4j, 4a, 4q, 4t, and 4g have shown stable binding interaction with streptomycin drug with active site of the B-DNA (PDB ID: 1BNA). The antibacterial activity, and molecular docking studies of the title compounds were suggested that these are promising anti-bacterial active skeletons.