Serendipitous identification of phenylhydrazine derivatives as potent inhibitors of carbapenem-resistant .

In the authors' previous study, 4-(2-((3-methyl-4-oxo-2-thioxo/dioxothiazolidin-5-ylidene) methyl) hydrazineyl) benzonitriles were found to demonstrate potent antibacterial activity against . Interestingly, the aforementioned compounds contain a 4-cyanophenylhydrazine motif. Intrigued by this observation, the authors focused on preparing a library of 4-cyanophenylhydrazine derivatives and studied their detailed antibacterial potential. This study led to the identification of a 4-cyanophenylhydrazine with potent inhibitory activity against carbapenem-resistant BAA-1605, with minimum inhibitory concentration (MIC) of 0.25 μg/ml and highest selectivity index of 640. The compound also demonstrated potent inhibition against multidrug-resistant isolates (MIC: 0.25-1 μg/ml). The identified 4-cyanophenylhydrazine compound exhibited synergistic activity with amikacin, tobramycin and polymyxin B against carbapenem-resistant BAA-1605.