Benzophenone-nucleoside derivatives as telomerase inhibitors: Design, synthesis and anticancer evaluation in vitro and in vivo
Benzophenone-nucleoside derivatives as telomerase inhibitors: Design, synthesis and anticancer evaluation in vitro and in vivo
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作为端粒酶抑制剂的二苯甲酮核苷衍生物：设计、合成和体外和体内抗癌评价
DOI：
10.1016/j.ejmech.2016.09.011
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发表时间：
2016-11-29
影响因子：
6.7
通讯作者：
Yao, Qi Zheng
中科院分区：
文献类型：
--
作者：
Shi, Jing Bo;Chen, Liu Zeng;Yao, Qi Zheng
以端粒酶为基础，合成了13种新型的苯他汀片段连锁司他夫定衍生物（8a-8e和11a-11f）。通过NMR和TOF-HRMS对其结构进行了表征。筛选结果表明，部分化合物具有较好的体内和体外抗癌活性。其中，化合物8d对端粒酶表现出较高的抑制活性，对SGC-7901细胞表现出良好的抗增殖活性，IC50值为0.77 μ M，诱导细胞周期阻滞于G2期。对SGC-7901细胞有促进凋亡的作用，线粒体膜电位测定提示MMP的耗散可能参与了标题化合物诱导的细胞凋亡。体内研究表明，化合物8d具有较强的抗肿瘤活性，抑制肿瘤生长。(C) 2016 Elsevier Masson SAS。版权所有。
Based on telomerase, thirteen novel phenstatin moiety linked stavudine derivatives (8a-8e and 11a-11f) were synthesized. The structures were determined by NMR and TOF-HRMS. The screening results showed that some compounds had better anti-cancer activity in vivo and in vitro. Among them, Compound 8d showed high inhibitory activity against telomerase and showed good antiproliferative activity against SGC-7901 cell with IC50 value 0.77 mu M by inducing cell cycle arrest at G2 phase. It also could improve SGC-7901 cell apoptosis, mitochondrial membrane potential assay indicated that the dissipation of MMP might participate in apoptosis induced by title compound. In vivo studies showed that compound 8d displayed potent anticancer activity with inhibition tumor growth. (C) 2016 Elsevier Masson SAS. All rights reserved.