Discovery of novel phenylhydrazone-based oxindole-thiolazoles as potent antibacterial agents toward Pseudomonas aeruginosa

With the soaring of Bacterial infection and drug resistance, it is imperative to exploit new efficient Antibacterial agents. This work constructed a series of unique phenylhydrazone-based oxindole-thiolazoles to combat monstrous Bacterial resistance. Some target molecules showed potent Antibacterial activity, among which oxindole-thiolimidazole derived carboxyphenylhydrazone 4e exhibited an 8-fold stronger inhibitory ability than norfloxacin on the growth of P. aeruginosa, with MIC value of 1 μg/mL. Compound 4e with imperceptible hemolysis could hamper Bacterial biofilm formation and significantly impede the development of Bacterial resistance. Subsequent mechanism studies demonstrated that 4e could destruct Bacterial cytoplasmic membrane, causing the leakage of cellular contents (protein and nucleic acid). Moreover, metabolic stagnation and intracellular oxidative stress caused by 4e expedited the death of bacteria. Furthermore, molecule 4e existed supramolecular interactions with DNA to block DNA proliferation. These research results provided a promising light for phenylhydrazone-based oxindole-thiolazoles as novel potential Antibacterial agents.