1,3-二氧六环连接的新型细菌拓扑异构酶抑制剂：扩展结构多样性和抗菌谱
1,3-Dioxane-Linked Novel Bacterial Topoisomerase Inhibitors: Expanding Structural Diversity and the Antibacterial Spectrum.
作者信息
Lu Yanran, Mann Chelsea A, Nolan Sheri, Collins Jessica A, Parker Elizabeth, Papa Jonathan, Vibhute Sandip, Jahanbakhsh Seyedehameneh, Thwaites Mary, Hufnagel David, Hazbón Manzour H, Moreno Jane, Stedman Timothy T, Wittum Thomas, Wozniak Daniel J, Osheroff Neil, Yalowich Jack C, Mitton-Fry Mark J
机构信息
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.
出版信息
ACS Med Chem Lett. 2022 May 9;13(6):955-963. doi: 10.1021/acsmedchemlett.2c00111. eCollection 2022 Jun 9.
Abstract
Antibacterial resistance continues its devastation of available therapies. Novel bacterial topoisomerase inhibitors (NBTIs) offer one solution to this critical issue. Two series of amine NBTIs bearing tricyclic DNA-binding moieties as well as amide NBTIs with a bicyclic DNA-binding moiety were synthesized and evaluated against methicillin-resistant (MRSA). Additionally, these compounds and a series of bicyclic amine analogues displayed high activity against susceptible and drug-resistant , expanding the spectrum of these dioxane-linked NBTIs.
摘要
抗菌耐药性持续破坏现有的治疗方法。新型细菌拓扑异构酶抑制剂（NBTIs）为这一关键问题提供了一种解决方案。合成了带有三环DNA结合部分的两类胺类NBTIs以及带有双环DNA结合部分的酰胺类NBTIs，并对耐甲氧西林金黄色葡萄球菌（MRSA）进行了评估。此外，这些化合物和一系列双环胺类似物对敏感菌和耐药菌均显示出高活性，扩大了这些二恶烷连接的NBTIs的抗菌谱。
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