Development of naphthalimide hydrazide derivatives as potent antibacterial agents against carbapenem-resistant A. baumannii†

In this work, a novel series of naphthalimide hydrazide derivatives were designed, synthesized and evaluated against a bacterial pathogen panel. Most of the compounds were found to exhibit potent antibacterial activity against carbapenem-resistant A. baumannii BAA 1605, with MIC ranging from 0.5 to 16 μg mL⁻¹. Compounds 5b, 5c, 5d and 5e showed the most potent antibacterial activity, with an MIC range of 0.5–1 μg mL⁻¹. These compounds were also found to be non-toxic to Vero cells with a high selectivity index. Further, they were active against 24 clinical isolates of MDR-AB with potent antibacterial activity. In addition, synergistic studies revealed that compound 5d exhibited synergism with FDA-approved drugs, as further validated through time-kill kinetic studies. These results highlight the potential of the synthesized compounds as promising leads for the development of novel and selective agents against carbapenem-resistant A. baumannii.