Title:A Review on Shikonin and its Derivatives as Potent Anticancer
Agents Targeted against Topoisomerases
Volume: 31
Issue: 8
关键词:
拓扑异构酶，抗癌药物，DNA可切割复合物，双拓扑抑制剂，紫草素及其衍生物，构效关系。
摘要: 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.
