文献类型：期刊文献

英文题名：Synthesis and biological evaluation of beta-lapachone-monastrol hybrids as potential anticancer agents

作者：Wu, Liqiang[1];Ma, Xin[1];Yang, Xiaojuan[2];Zhang, Chong[1]

第一作者：Wu, Liqiang

通讯作者：Wu, LQ[1]

机构：[1]Xinxiang Med Univ, Sch Pharm, Xinxiang 453003, Henan, Peoples R China;[2]Xinxiang Univ, Coll Chem & Chem Engn, Xinxiang 453003, Henan, Peoples R China

第一机构：Xinxiang Med Univ, Sch Pharm, Xinxiang 453003, Henan, Peoples R China

通讯机构：[1]corresponding author), Xinxiang Med Univ, Sch Pharm, Xinxiang 453003, Henan, Peoples R China.

年份：2020

卷号：203

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：;Scopus(收录号：2-s2.0-85087806156);WOS:【SCI-EXPANDED(收录号:WOS:000568867400026)】；

基金：This work is financially supported by NSFC-Henan Joint Fund (No. U1604164).

语种：英文

外文关键词：beta-Lapachone; Monastrol; Molecular hybridization; NQO1; Antitumor

摘要：A series of novel beta-lapachone analogs was designed and synthesized by replacing pyran ring of beta-lapachone with tetrahydropyrimidinethione moiety of monastrol. These hybrids had potent anti-proliferative activity against NQO1-rich cell lines (HepG2 and A549), while NQO1-defficient cell lines (H596 and LO2) were less sensitive to these hybrids. Dicoumarol partially inhibited the activity of these compounds against A549 cell lines, indicating that the activation of biological reduction mediated by NQO1 might partly affect the antiproliferative effects. NQO1 assay and docking study demonstrated 4j was a good substrate of NQO1. Furthermore, as suggested by cellular mechanistic research concerning antitumor activity, the representative compound 4j resulted in ROS production depending on NQO1, then oxidative stress triggered apoptotic cell death. Importantly, 4j significantly suppressed cancer growth in HepG2 xenograft models without obvious toxicity, suggesting that 4j deserve further research as potent antitumor agents for cancer therapy. (C) 2020 Elsevier Masson SAS. All rights reserved.