期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 193, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2020.112222
关键词
Macrolide; Quinolone; Hybrid; Dual modes of action; Ribosome; Topoisomerase
资金
- National Natural Science Foundation of China [81761128016, 8187131584, 81673335, 21878022]
- National Key Research and Development Program of China [2018YFA0901800]
- China Scholarship Council
In the search for novel hybrid molecules by fusing two biologically active scaffolds into one heteromeric chemotype, we found that hybrids of azithromycin and ciprofloxacin/gatifloxacin 26j and 26l can inhibit the supercoiling activity of E. coli gyrase by poisoning it in a way similar to fluoroquinolones. This may modestly contribute to their potencies, which are equal to ciprofloxacin against constitutively resistant Staphylococcus aureus, whose growth is not inhibited by the presence of macrolides. In contrast, introduction of quinolines (the 3-quinoline 26b and the 6-quinoline 26o) with an optimized rigid spacer at the 6-OH of azithromycin acylides did not exert significant potency against constitutively resistant S. aureus, despite the fact that the quinoline-containing compounds, exemplified by 26o, were as active as telithromycin against susceptible, inducibly- and efflux-resistant pathogens. The novel dual modes of action involving protein synthesis inhibition and poisoning DNA replication may pave the way for restoration of antibacterial activities of the current macrolides against constitutively resistant clinical isolates. (c) 2020 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据