A Review on Shikonin and its Derivatives as Potent Anticancer Agents Targeted against Topoisomerases

拓扑异构酶 喜树碱 化学 药理学 细胞毒性 拓扑异构酶抑制剂 天然产物 抗癌药 药品 生物化学 生物 体外
作者
Olagoke Zacchaeus Olatunde,Jianping Yong,Can‐Zhong Lu,Yanlin Ming
出处
期刊:Current Medicinal Chemistry [Bentham Science Publishers]
卷期号:31 (8): 920-937 被引量:6
标识
DOI:10.2174/0929867330666230208094828
摘要

Abstract: The topoisomerases (TOPO) play indispensable roles in DNA metabolism, by regulating the topological state of DNA. Topoisomerase I and II are the well-established drug-targets for the development of anticancer agents and antibiotics. These drugs-targeting enzymes have been used to establish the relationship between drug-stimulated DNA cleavable complex formation and cytotoxicity. Some anticancer drugs (such as camptothecin, anthracyclines, mitoxantrone) are also widely used as Topo I and Topo II inhibitors, but the poor water solubility, myeloma suppression, dose-dependent cardiotoxicity, and multidrug resistance (MDR) limited their prolong use as therapeutics. Also, most of these agents displayed selective inhibition only against Topo I or II. In recent years, researchers focus on the design and synthesis of the dual Topo I and II inhibitors, or the discovery of the dual Topo I and II inhibitors from natural products. Shikonin (a natural compound with anthraquinone skeleton, isolated from the roots of Lithospermum erythrorhizon) has drawn much attention due to its wide spectrum of anticancer activities, especially due to its dual Topo inhibitive performance, and without the adverse side effects, and different kinds of shikonin derivatives have been synthesized as TOPO inhibitors for the development of anticancer agents. In this review, the progress of the shikonin and its derivatives together with their anticancer activities, anticancer mechanism, and their structure-activity relationship (SAR) was comprehensively summarized by searching the CNKI, PubMed, Web of Science, Scopus, and Google Scholar databases.
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