New Coumarin–Malonylurea Conjugates as Potent Antituberculosis Agents: Cytotoxicity and Docking Studies

With the intent to discover new antituberculosis agents, coumarin‐malonylurea conjugates were developed. Structures of newly synthesized compounds were characterized by elemental and spectroscopic analysis. In vitro antitubercular activity of all the compounds was assessed and the most effective compounds were evaluated for cytotoxicity assay with Vero cells. Among the synthesized, compound 1‐benzyl‐3‐((6‐methyl‐2‐oxo‐2H‐chromen‐4‐yl)methyl)‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trione was found to be 2.63 times more active than the standard drug Pyrazinamide. Molecular docking on Mycobacterium tuberculosis InhA bound to NITD‐916 (PDB: 4R9S) revealed that compounds possessed greater binding affinity towards proteins. In addition, the most active compounds exhibited high levels of interaction with the target protein and exceptional safety profile, suggesting they may prove to be effective leads for new drugs.