Discovery of 3-peptide substituted arenobufagin derivatives as potent antitumor agents with low cardiotoxicity
Discovery of 3-peptide substituted arenobufagin derivatives as potent antitumor agents with low cardiotoxicity
复制标题
发现 3 肽取代的沙蚕精衍生物作为具有低心脏毒性的有效抗肿瘤剂
DOI：
10.1016/j.steroids.2020.108772
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发表时间：
2021-02-01
期刊：
影响因子：
2.7
通讯作者：
Wu, Yuelin
中科院分区：
文献类型：
--
作者：
Chen, Baobao;Wang, Chuanhao;Wu, Yuelin
活性天然产物可能是有价值的先导化合物，许多天然产物衍生的药物已成功进入临床。华蟾素是蟾毒的重要活性成分之一，具有较强的心脏毒性，具有较强的抗肿瘤活性，但其临床前开发受到限制。设计并合成了10个3-单肽取代的华蟾素衍生物。抗肿瘤活性和心脏毒性试验表明，化合物ZM226是一种心脏毒性较低的有效抗肿瘤药物。这些发现表明，优化3位上的Arenobufagin可能是开发基于Arenobufagin的抗肿瘤候选药物的有效策略。
Active natural productscan be valuable lead compounds and numerous drugs derived from natural products have successfully entered the clinic. Arenobufagin, one of the important active components of toad venom, indicates significant antitumor activities with limited preclinical development for its strong cardiotoxicity. Ten 3-monopeptide substituted arenobufagin derivatives have been designed and synthesized. Antitumor activity and cardiotoxicity assays lead to the discovery of compound ZM226 as a potent antitumor agent with low cardiotoxicity. These findings suggest optimization of arenobufagin on position 3 maybe an efficacious strategy for the development of antitumor drug candidates derived from arenobufagin.