Synthesis, Antimicrobial and Antibiofilm Activities, and Molecular Docking Investigations of 2-(1 H -Indol-3-yl)-1 H -benzo[ d ]imidazole Derivatives.

The treatment of many bacterial and fungal infections remains a problem due to increasing antibiotic resistance and biofilm formation by pathogens. In the present article, a methodology for the chemoselective synthesis of 2-(1 H -indol-3-yl)-1 H -benzo[ d ]imidazole derivatives is presented. We report on the antimicrobial activity of synthesized 2-(1 H -indol-3-yl)-1 H -benzo[ d ]imidazoles with significant activity against Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 43300 (MRSA), Mycobacterium smegmatis (mc(2)155/ATCC 700084), and Candida albicans ATCC 10231. High activity against staphylococci was shown by indolylbenzo[ d ]imidazoles 3ao and 3aq (minimum inhibitory concentration (MIC) < 1 µg/mL) and 3aa and 3ad (MIC 3.9-7.8 µg/mL). A low MIC was demonstrated by 2-(1 H -indol-3-yl)-1-methyl-1 H -benzo[ d ]imidazole ( 3ag ) against M. smegmatis and against C. albicans (3.9 µg/mL and 3.9 µg/mL, respectively). 2-(5-Bromo-1 H -indol-3-yl)-6,7-dimethyl-1 H -benzo[ d ]imidazole ( 3aq ) showed a low MIC of 3.9 µg/mL against C. albicans . Compounds 3aa , 3ad , 3ao , and 3aq exhibited excellent antibiofilm activity, inhibiting biofilm formation and killing cells in mature biofilms. Molecular docking analysis identified three potential interaction models for the investigated compounds, implicating (p)ppGpp synthetases/hydrolases, FtsZ proteins, or pyruvate kinases in their antibacterial action mechanism.