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

The emergence of antibiotic resistance to S. aureus and M. tuberculosis , 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 E. coli , S. aureus , K. pneumoniae , P. aeruginosa , A. baumannii 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 S. aureus with MIC 0.03-8 μg mL −1 . In addition, these compounds have also exhibited potent inhibition against MDR strains of S. aureus , including VRSA with MICs 0.06-4 μg mL −1 . Compounds 4h , 4j , 4l , 4m , 4q , 4r , 9a , 9b , 9c , 9d , 9e , 9g , 9h , 9j , 13f and 17e also exhibited good antimycobacterial activity against M. tuberculosis with MIC 2-64 μg mL −1 . 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, in silico studies were performed to decipher the possible mechanism of action. Comprehensively, these results highlight the potential of naphthalimide-thiourea derivatives as promising antibacterial agents. Novel series of naphthalimide thiourea derivatives were synthesised and evaluated against bacterial pathogen panel and mycobacterial pathogen panel.