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.

随着细菌感染和耐药性的飙升，开发新的高效抗菌药物势在必行。这项工作构建了一系列独特的基于苯腙的羟吲哚-硫醇唑来对抗巨大的细菌耐药性。部分靶分子具有较强的抗菌活性，其中羟吲哚-硫咪唑衍生的羧基苯腙4e对铜绿假单胞菌的生长抑制能力是诺氟沙星的8倍，MIC值为1 μg/mL。具有不易察觉的溶血的化合物4e会阻碍细菌生物膜的形成，并显着阻碍细菌耐药性的发展。随后的机制研究表明，4e可破坏细菌细胞质膜，导致细胞内容物（蛋白质和核酸）泄漏。此外， 4e引起的代谢停滞和细胞内氧化应激加速了细菌的死亡。此外，分子4e与DNA存在超分子相互作用以阻断DNA增殖。这些研究结果为苯腙基羟吲哚-硫唑唑类作为新型潜在抗菌剂提供了有希望的启示。