Synthesis and biological evaluation of new naphthalimide-thiourea derivatives as potent antimicrobial agents active against multidrug-resistant Staphylococcus aureus and Mycobacterium tuberculosis

The emergence of antibiotic resistance to and , particularly MRSA, VRSA, and drug-resistant tuberculosis, poses a serious threat to human health. Towards discovering new antibacterial agents, we designed and synthesized a series of new naphthalimide-thiourea derivatives and evaluated them against a panel of bacterial strains consisting of , , , , and various mycobacterial pathogens. Compounds 4a, 4l, 4m, 4n, 4q, 9f, 9l, 13a, 13d, 13e, 17a, 17b, 17c, 17d, and 17e demonstrated potent antibacterial activity against with MIC 0.03-8 μg mL . In addition, these compounds have also exhibited potent inhibition against MDR strains of , including VRSA with MICs 0.06-4 μg mL . Compounds 4h, 4j, 4l, 4m, 4q, 4r, 9a, 9b, 9c, 9d, 9e, 9g, 9h, 9j, 13f and 17e also exhibited good antimycobacterial activity against with MIC 2-64 μg mL . The cytotoxicity assay using Vero cells revealed that all the compounds were non-toxic and exhibited a favorable selectivity index (SI >40). Time kill kinetics data indicated that compounds exhibited concentration-dependent killing. Furthermore, studies were performed to decipher the possible mechanism of action. Comprehensively, these results highlight the potential of naphthalimide-thiourea derivatives as promising antibacterial agents.