DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.

DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.
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DOI:
10.1016/j.chembiol.2010.04.012
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发表时间:
2010-05-28
影响因子:
--
通讯作者:
Marchand C
Marchand C
中科院分区:
生物1区
文献类型:
--
作者:
Pommier Y;Leo E;Zhang H;Marchand C

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DNA拓扑异构酶是重要的抗癌和抗菌药物的靶标。临床开发中的喜树碱和新型非喜树碱(茚并异喹啉和 ARC-111)以真核 IB 型拓扑异构酶(Top1)为靶点,而人 IIA 型拓扑异构酶(Top2α 和 Top2β)是广泛使用的抗癌药物依托泊苷、蒽环类药物(阿霉素、柔红霉素)和米托蒽醌的靶点。细菌 II 型拓扑异构酶(旋转酶和拓扑 IV)是喹诺酮类和氨基香豆素抗生素的靶标。本综述重点关注拓扑异构酶及其抑制剂的分子和生化特征。我们还讨论了拓扑异构酶毒物通过界面抑制和拓扑异构酶裂解复合物捕获的常见作用机制。
DNA topoisomerases are the targets of important anticancer and antibacterial drugs. Camptothecins and novel noncamptothecins in clinical development (indenoisoquinolines and ARC-111) target eukaryotic type IB topoisomerases (Top1), whereas human type IIA topoisomerases (Top2α and Top2β) are the targets of the widely used anticancer agents etoposide, anthracyclines (doxorubicin, daunorubicin), and mitoxantrone. Bacterial type II topoisomerases (gyrase and Topo IV) are the targets of quinolones and aminocoumarin antibiotics. This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors. We also discuss the common mechanism of action of topoisomerase poisons by interfacial inhibition and trapping of topoisomerase cleavage complexes.
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影响因子: 14.9
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