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-indol-3-yl)-1-benzo[]imidazole derivatives is presented. We report on the antimicrobial activity of synthesized 2-(1-indol-3-yl)-1-benzo[]imidazoles with significant activity against ATCC 25923, ATCC 43300 (MRSA), (mc(2)155/ATCC 700084), and ATCC 10231. High activity against staphylococci was shown by indolylbenzo[]imidazoles and (minimum inhibitory concentration (MIC) < 1 µg/mL) and and (MIC 3.9-7.8 µg/mL). A low MIC was demonstrated by 2-(1-indol-3-yl)-1-methyl-1-benzo[]imidazole () against and against (3.9 µg/mL and 3.9 µg/mL, respectively). 2-(5-Bromo-1-indol-3-yl)-6,7-dimethyl-1-benzo[]imidazole () showed a low MIC of 3.9 µg/mL against . Compounds , , , and 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.