Developments in Non-Intercalating Bacterial Topoisomerase Inhibitors: Allosteric and ATPase Inhibitors of DNA Gyrase and Topoisomerase IV.
Developments in Non-Intercalating Bacterial Topoisomerase Inhibitors: Allosteric and ATPase Inhibitors of DNA Gyrase and Topoisomerase IV.
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DOI：
10.3390/ph16020261
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发表时间：
2023-02-08
期刊：
影响因子：
4.6
通讯作者：
McPhillie, Martin J.
中科院分区：
文献类型：
--
作者：
Grossman, Scott;Fishwick, Colin W. G.;McPhillie, Martin J.
抗生素使用的增加和抗生素耐药性的发生导致许多一线抗生素治疗的有效性急剧降低。拓扑异构酶抑制剂包括氟喹诺酮类是用于治疗一系列感染的广谱抗生素，其通过嵌入结合的DNA来稳定拓扑异构酶-DNA切割复合物。然而，这些都受到细菌耐药性，主要是在活性位点的单核苷酸多态性的形式。已经进行了重要的研究，寻找能够在氟喹诺酮结合位点远端抑制细菌拓扑异构酶的新型生物活性分子。值得注意的是，研究人员已经开始寻找可以通过替代机制抑制拓扑异构酶的抗感染药物。本文综述了主要通过非嵌入剂抑制拓扑异构酶的工作，包括那些作用于一个新的变构位点，ATP酶结构域抑制剂，以及那些提供独特的结合模式和作用机制。
Increases in antibiotic usage and antimicrobial resistance occurrence have caused a dramatic reduction in the effectiveness of many frontline antimicrobial treatments. Topoisomerase inhibitors including fluoroquinolones are broad-spectrum antibiotics used to treat a range of infections, which stabilise a topoisomerase-DNA cleavage complex via intercalation of the bound DNA. However, these are subject to bacterial resistance, predominantly in the form of single-nucleotide polymorphisms in the active site. Significant research has been undertaken searching for novel bioactive molecules capable of inhibiting bacterial topoisomerases at sites distal to the fluoroquinolone binding site. Notably, researchers have undertaken searches for anti-infective agents that can inhibit topoisomerases through alternate mechanisms. This review summarises work looking at the inhibition of topoisomerases predominantly through non-intercalating agents, including those acting at a novel allosteric site, ATPase domain inhibitors, and those offering unique binding modes and mechanisms of action.
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抗菌QPT-1，抗癌药物依托泊苷和莫西沙星抑制DNA循环酶的结构基础。
影响因子：
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