Isodiospyrin is a natural product from the plant Diospyros morrisiana, which consists of an asymmetrical 1,2-binaphthoquinone chromophore. Isodiospyrin exhibits cytotoxic activity to tumor cell lines but very little is known about its cellular target and mechanism of action. Unlike the prototypic human topoisomerase I (htopo I) poison camptothecin, isodiospyrin does not induce htopo I-DNA covalent complexes. However, isodiospyrin antagonizes camptothecin-induced, htopo I-mediated DNA cleavage. Binding analysis indicated that isodiospyrin binds htopo I but not DNA. These results suggest that isodiospyrin inhibits htopo I by direct binding to htopo I, which limits htopo I access to the DNA substrate. Furthermore, isodiospyrin exhibits strong inhibitory effect on the kinase activity of htopo I toward splicing factor 2/alternate splicing factor in the absence of DNA. Thus, these findings have important implications on naphthoquinone and its derivatives' cellular mode of actions, i.e. these novel DNA topoisomerase I inhibitors can prevent both DNA relaxation and kinase activities of htopo I.

中文翻译：

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异渗糖蛋白是一种新型的人类DNA拓扑异构酶I抑制剂。

异鬼皮草苷是一种来自植物Diospyros morrisiana的天然产物，它由不对称的1,2-联萘醌生色团组成。异嘧啶对肿瘤细胞系表现出细胞毒活性，但对其细胞靶标和作用机理知之甚少。与原型人拓扑异构酶I（htopo I）对喜树碱的毒性不同，异二嘧啶不会诱导htopo I-DNA共价复合物。但是，异嘧啶可拮抗喜树碱诱导的，htopo I介导的DNA切割。结合分析表明异嘧啶可结合htopo I，但不结合DNA。这些结果表明，异鬼皮苷通过直接结合至htopo I抑制了htopo I，这限制了htopo I对DNA底物的访问。此外，在不存在DNA的情况下，异二嘧啶对htopo I的针对剪接因子2 /其他剪接因子的激酶活性表现出强烈的抑制作用。因此，这些发现对萘醌及其衍生物的细胞作用方式具有重要意义，即这些新型的DNA拓扑异构酶I抑制剂可防止htopo I的DNA松弛和激酶活性。