Beijing Key Laboratory of Plant Resource Research and Development, College of Chemical and Environmental Engineering, Beijing Technology and Business University, Beijing, China.
Pharm Biol. 2011 Aug;49(8):796-9. doi: 10.3109/13880209.2010.548817. Epub 2011 Apr 15.
DNA topoisomerase I (topo I) is an essential enzyme which regulates the conformational changes in DNA topology by cleaving and rejoining DNA strands during normal cell growth. The inhibitors of topo I represent a major class of anticancer drugs. In our projects to isolate new anticancer agents from marine-derived fungi, secalonic acid D (SAD) with inhibitory activity on topo I was isolated from the fermentation broth of marine lichen-derived fungus Gliocladium sp. T31, which was collected from marine sediments in South Pole.
The inhibitory activity of SAD on topo I was investigated for the first time.
The inhibitory effect of SAD on topo I was determined via in vitro supercoil relaxation assays and electrophoretic mobility shift assay (EMSA) using plasmid substrate, pBR322.
SAD displays a considerable inhibition on topo I in a dose-dependent manner with the minimum inhibitory concentration (MIC) of 0.4 µM. Unlike the prototypic DNA topo I poison camptothecin (CPT), SAD inhibits the binding of topo I to DNA but does not induce the formation of topo I-DNA covalent complexes.
SAD is an excellent topo I inhibitor and thus a significantly potential anticancer candidate.
DNA 拓扑异构酶 I（topo I）是一种必需的酶，它通过在正常细胞生长过程中切割和重新连接 DNA 链来调节 DNA 拓扑结构的构象变化。topo I 的抑制剂是一类主要的抗癌药物。在我们从海洋来源的真菌中分离新的抗癌剂的项目中，从南极海洋沉积物中采集的海洋地衣来源真菌Gliocladium sp. T31 的发酵液中分离到了具有 topo I 抑制活性的 secalonic 酸 D（SAD）。
首次研究了 SAD 对 topo I 的抑制活性。
通过体外超螺旋松弛测定和电泳迁移率变动分析（EMSA）用质粒底物 pBR322 测定 SAD 对 topo I 的抑制作用。
SAD 以剂量依赖性方式对 topo I 显示出相当的抑制作用，最小抑制浓度（MIC）为 0.4µM。与典型的 DNA topo I 毒物喜树碱（CPT）不同，SAD 抑制 topo I 与 DNA 的结合，但不诱导 topo I-DNA 共价复合物的形成。
SAD 是一种优秀的 topo I 抑制剂，因此是一种很有潜力的抗癌候选药物。
