Ligand Free Palladium Catalyzed Synthesis of 3‐Aryl/heteroaryl‐4‐Indolylmaleimide and its Antimicrobial Activity.

Here we have developed ligand free palladium catalyzed Suzuki coupling of 3‐bromo‐1‐methyl‐4‐indolylmaleimide under room temperature condition. Twenty unsymmetrical indolylmaleimide derivatives ( 4 a ‐ 4 t ) were synthesised using various aryl‐ and heteroarylboronic acids in good to excellent yields. Synthesised compounds were further screened for its antimicrobial activity. Compounds 4 q displayed significant minimum inhibitory concentration (MIC) value of 2.3µM toward S. aureus . 4 q was also found to be bactericidal in nature with minimum bactericidal concentration (MBC) value of 4.6 µM. The selective index calculated for compounds 4 q was 38.84 towards S. aureus . Compound 4 s was found to be active against M. Tuberculosis and 3.5 times more efficacious than standard drug rifampicin against multidrug‐resistant Mycobacterium tuberculosis (MDR‐MT) strain. In mechanistic study, we identified that 4 s is active in Shikimate kinase enzyme inhibition assay.