Serendipitous identification of phenylhydrazine derivatives as potent inhibitors of carbapenem-resistant Acinetobacter baumannii

Abstract

Background: 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 Acinetobacter baumannii. Interestingly, the aforementioned compounds contain a 4-cyanophenylhydrazine motif. Materials & methods: Intrigued by this observation, the authors focused on preparing a library of 4-cyanophenylhydrazine derivatives and studied their detailed antibacterial potential. Results: This study led to the identification of a 4-cyanophenylhydrazine with potent inhibitory activity against carbapenem-resistant A. baumannii 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 A. baumannii isolates (MIC: 0.25–1 μg/ml). Conclusion: The identified 4-cyanophenylhydrazine compound exhibited synergistic activity with amikacin, tobramycin and polymyxin B against carbapenem-resistant A. baumannii BAA-1605.