Seventeen novel derivatives of (Z)-methyl 3-(4-oxo-2-thioxothiazolidin-5-ylidene)methyl)-1H-indole-2-carboxylate were synthesized and tested for antimicrobial properties. These compounds demonstrated remarkably potent antibacterial activity against eight different bacterial strains, significantly outperforming the standard antibiotics ampicillin and streptomycin by factors of 10 to 50. Compound 8 was identified as the most effective antibacterial agent. Furthermore, the compounds showed good to excellent antifungal activity, with Compound 15 being the most potent against various fungi. Computational docking studies suggest the antibacterial mechanism involves inhibiting the E. coli MurB enzyme, and the antifungal action is likely due to the inhibition of the CYP51Ca lanosterol 14α\alphaα-demethylase. Preliminary studies on drug-likeness, ADMET properties, and cytotoxicity against normal human cells (MRC5) were also completed.
