A class of unique hydrazyl hydroxycoumarins (HHs) as novel structural scaffold was developed to combat dreadful bacterial infections. Some HHs could effectively suppress bacterial growth at low concentrations, especially, pyridyl HH exhibited a good inhibition against 27853 with a low MIC value of 0.5 μg/mL, which was 8-fold more active than norfloxacin. Furthermore, pyridyl HH with low hemolytic activity and low cytotoxicity towards NCM460 cells showed much lower trend to induce the drug-resistant development than norfloxacin. Preliminarily mechanism exploration indicated that pyridyl HH could eradicate the integrity of bacterial membrane, result in the leakage of intracellular proteins, and interact with bacterial DNA gyrase non-covalent binding, and ADME analysis manifested that compound gave good pharmacokinetic properties. These results suggested that the newly developed hydrazyl hydroxycoumarins as potential multitargeting antibacterial agents should be worthy of further investigation for combating bacterial infection.

中文翻译：

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肼基羟基香豆素是铜绿假单胞菌新的潜在征服者

一类独特的肼基羟基香豆素（HH）作为新型结构支架被开发用于对抗可怕的细菌感染。一些HH在低浓度下即可有效抑制细菌生长，特别是吡啶基HH对27853具有良好的抑制作用，其MIC值为0.5 μg/mL，其活性是诺氟沙星的8倍。此外，吡啶基HH具有低溶血活性和对NCM460细胞的低细胞毒性，其诱导耐药性发展的趋势比诺氟沙星低得多。初步的机制探索表明，吡啶基HH可以破坏细菌膜的完​​整性，导致细胞内蛋白质的渗漏，并与细菌DNA旋转酶非共价结合，ADME分析表明该化合物具有良好的药代动力学特性。这些结果表明，新开发的肼基羟基香豆素作为潜在的多靶点抗菌剂应该值得进一步研究以对抗细菌感染。