化学
活动站点
大肠杆菌
抗生素
抗菌活性
维罗细胞
酶
细菌
立体化学
细胞毒性
结构-活动关系
体外
生物化学
组合化学
生物
基因
遗传学
作者
N. Segretti,Ricardo Augusto Massarico Serafim,Mariana C. F. Segretti,Masanobu Miyata,Fernando Rodrigues Coelho,Ohára Augusto,Elizabeth Igne Ferreira
标识
DOI:10.1016/j.bmcl.2016.06.089
摘要
The development of resistance to antibiotics by microorganisms is a major problem for the treatment of bacterial infections worldwide, and therefore, it is imperative to study new scaffolds that are potentially useful in the development of new antibiotics. In this regard, we propose the design, synthesis and biological evaluation of hybrid sulfonylhydrazone bioisosters/furoxans with potential antibacterial (Escherichia coli) activity. The most active compound of the series, (E)-3-methyl-4-((2-tosylhydrazono)methyl)-1,2,5-oxadiazole 2-oxide, with a MIC=0.36μM, was not cytotoxic when tested on Vero cells (IC50>100μM). To complement the in vitro screening, we also studied the interaction of the test compounds with β-ketoacyl acyl carrier protein synthase (FabH), the target for the parent compounds, and we observed three important hydrogen-bonding interactions with two important active site residues in the catalytic site of the enzyme, providing complementary evidence to support the target of the new hybrid molecules.
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