Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source.
Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source.
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DOI：
10.1021/np000058r
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发表时间：
2000-07
影响因子：
5.1
通讯作者：
Bing-Nan Zhou;Jeannine M. Hoch;Randall K. Johnson;Michael R. Mattern;Wai-Kwong Eng;Ji Ma;Sidney M. H
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文献类型：
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作者：
Bing-Nan Zhou;Jeannine M. Hoch;Randall K. Johnson;Michael R. Mattern;Wai-Kwong Eng;Ji Ma;Sidney M. H
使用喜树碱作为参考点，通过COMPARE方案对来自美国国家癌症研究所活性库的提取物的细胞毒性数据进行分析。通过该方法鉴定的提取物进一步通过拓扑异构酶I抑制剂的选择性酵母生物测定和稳定拓扑异构酶I-DNA共价二元复合物的化合物的生物化学测定来表征。5种提取物在酵母生物测定中呈阳性，8种提取物在监测拓扑异构酶I-DNA复合物稳定性的测定中显示活性。后一种提取物中有四种在酵母生物测定中无活性，因此在没有比较预选过程的情况下不会被鉴定为命中。其中一个提取物，从Pyrenacantha klaineana，被选中进行详细的研究，并分级分离，这种提取物产生喜树碱和9-甲氧基喜树碱的生物活性成分。
Analysis of cytotoxicity data of extracts from the National Cancer Institute's Active Repository by the COMPARE protocol was carried out using camptothecin as a reference point. Extracts identified by this process were further characterized by a selective yeast bioassay for inhibitors of topoisomerase I and by a biochemical assay for compounds that stabilize the topoisomerase I-DNA covalent binary complex. Five of the extracts were positive in the yeast bioassay, and eight extracts showed activity on the assay that monitors stabilization of the topoisomerase I-DNA complex. Four of the latter extracts were inactive in the yeast bioassay, and thus would not have been identified as hits without the COMPARE preselection process. One of the extracts, from Pyrenacantha klaineana, was selected for detailed investigation, and fractionation of this extract yielded camptothecin and 9-methoxycamptothecin as the bioactive constituents.