Antitumor agents. Part 235: Novel 4'-ester etoposide analogues as potent DNA topoisomerase II inhibitors with improved therapeutic potential.
Antitumor agents. Part 235: Novel 4'-ester etoposide analogues as potent DNA topoisomerase II inhibitors with improved therapeutic potential.
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抗肿瘤剂。
DOI：
10.1016/j.bmc.2004.03.056
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Lee,Kuo-Hsiung
中科院分区：
文献类型：
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作者：
Xiao,Zhiyan;Vance,JohnR;Bastow,KennethF;Brossi,Arnold;Wang,Hui-Kang;Lee,Kuo-Hsiung
以克服耐药和提高水溶性为目的，设计合成了8种4′-酯类鬼臼毒素衍生物（9-16）。这些化合物在引起细胞蛋白链DNA断裂和抑制KB和1抗性KB-7d细胞复制方面优于依托opo苷(1)。化合物9和10对DNA拓扑异构酶II具有明显的体外抑制活性。化合物10也表现出类似于GL-331的体外DNA切割模式(5)。在此基础上提出了1-类似物作用模式的假设模型。
Eight 4′-ester epipodophyllotoxin derivatives (9–16) were designed and synthesized with the aim to overcome drug-resistance and improve water-solubility simultaneously. These compounds were superior to etoposide (1) in causing cellular protein-linked DNA breaks and inhibiting KB and 1-resistant KB-7d cell replication. Compounds 9 and 10 showed significant inhibitory activity against DNA topoisomerase II in vitro. Compound 10 also exhibited an in vitro DNA cleavage pattern similar to that of GL-331 (5). A hypothetical model on the action mode of 1-analogues is proposed based on the results.