Novel Naphthalimide Aminothiazoles as Potential Multitargeting Antimicrobial Agents.

A series of novel naphthalimide aminothiazoles were developed for the first time and evaluated for their antimicrobial activity. Some prepared compounds possessed good inhibitory activity against the tested bacteria and fungi. Noticeably, the piperazine derivative displayed superior antibacterial activity against MRSA and with MIC values of 4 and 8 μg/mL, respectively, to reference drugs. The most active compound showed low toxicity against mammalian cells with no obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy and efficient membrane permeability. Preliminarily investigations revealed that compound could not only bind with gyrase-DNA complex through hydrogen bonds but could effectively intercalate into MRSA DNA to form -DNA supramolecular complex, which might be responsible for the powerful bioactivity. Further transportation behavior evaluation indicated that molecule could be effectively stored and carried by human serum albumin, and the hydrophobic interactions and hydrogen bonds played important roles in the binding process.