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.