芳香霉素对非洲锥虫的活性。
Activity of Aromathecins against African Trypanosomes.
机构信息
Division of Clinical Pharmacology, Departments of Medicine and of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA.
出版信息
Antimicrob Agents Chemother. 2018 Oct 24;62(11). doi: 10.1128/AAC.00786-18. Print 2018 Nov.
Abstract
African sleeping sickness is responsible for thousands of deaths annually, and new therapeutics are needed. This study evaluated aromathecins, experimental inhibitors of mammalian topoisomerase IB, against African trypanosomes. The compounds had selectively toxic antiparasitic potency, poisoning activity against the phylogenetically unique topoisomerase in these parasites, and a representative compound intercalated into DNA with micromolar affinity. DNA intercalation and topoisomerase poisoning may contribute to the antitrypanosomal activity of aromathecins.
摘要
非洲昏睡病每年导致数千人死亡，因此需要新的治疗方法。本研究评估了芳香酶抑制剂，这是一种实验性的哺乳动物拓扑异构酶 IB 抑制剂，针对非洲锥虫。这些化合物具有选择性的有毒抗寄生虫活性，对这些寄生虫中独特的拓扑异构酶具有毒性作用，并且一种代表性的化合物以微摩尔亲和力嵌入 DNA 中。DNA 嵌入和拓扑异构酶中毒可能是芳香酶抑制剂抗锥虫活性的原因。
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