高等学校化学学报 ›› 2016, Vol. 37 ›› Issue (12): 2159-2167.doi: 10.7503/cjcu20160568

• 有机化学 • 上一篇    下一篇

大黄酸-缬氨酸加合物的合成及初步抗肿瘤活性

张洁, 周昌健, 谢建伟(), 代斌   

  1. 石河子大学化学化工学院, 新疆兵团化工绿色过程重点实验室-省部共建国家重点实验室培育基地, 石河子832003
  • 收稿日期:2016-08-11 出版日期:2016-12-10 发布日期:2016-11-15
  • 作者简介:联系人简介: 谢建伟, 男, 博士, 副教授, 主要从事药物化学研究. E-mail:cesxjw@foxmail.com
  • 基金资助:
    国家自然科学基金(批准号: 21606153)和石河子大学优秀青年科技人才培育计划(批准号: 2013ZRKXYQ-YD01)资助

Synthesis and Antitumor Activities of Rhein-Valine Adducts

ZHANG Jie, ZHOU Changjian, XIE Jianwei*(), DAI Bin   

  1. School of Chemistry and Chemical Engineering, Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, Shihezi 832003, China
  • Received:2016-08-11 Online:2016-12-10 Published:2016-11-15
  • Contact: XIE Jianwei E-mail:cesxjw@foxmail.com
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No.21606153) and the Outstanding Youth Project of Shihezi University, China(No.2013ZRKXYQ-YD01)

摘要:

以大黄酸为原料, 经酯化、 烷基化、 水解及缩合等反应步骤合成了12个大黄酸-缬氨酸加合物. 目标化合物经1H NMR, 13C NMR和HRMS进行了结构确证. 以顺铂和阿霉素为阳性对照药, 采用四甲基偶氮唑盐(MTT)法考察了目标化合物的体外抗肿瘤(Hela, MCF-7, HepG2, KB和HEK293T等5株细胞)活性. 结果表明, 化合物5l显示出较好的抗肿瘤活性, 其IC50值在1.6~9.4 μmol/L之间. 作用机制研究结果表明, 化合物5l能够与DNA发生较强的结合作用.

关键词: 大黄酸, 缬氨酸, 加合物, 抗肿瘤活性, 构效关系

Abstract:

In order to search for novel leading compounds endowed with better antitumor activities, twelve novel rhein-valine derivatives were designed and synthesized by modification of position-1, 3 and 8 of rhein nucleus, and their structures were confirmed by 1H NMR, 13C NMR and HRMS. All the target compounds were tested for cytotoxic activity against five cancer cell lines including Hela, MCF-7, HepG2, KB and HEK293T by methyl thiazolyl tetrazolium(MTT) method in vitro. The results demonstrate that compound 5l displayed a broad spectrum of cytotoxic activities with IC50 value of lower than 10 μmol/L against all tumor cell lines, compounds 5e, 5i and 5j only demonstrated moderate cytotoxic activities(IC50<50 μmol/L). Primary structure-activity relationships(SARs) analysis indicated that the 3-phenylpropoxyl substituents in position-1,8 of rhein nucleus were the suitable pharmacophoric group giving rise to significant antitumor agents. In addition, compound 5l was found to exhibit remarkable DNA intercalating effects.

Key words: Rhein, Valine, Adduct, Antitumor activity, Structure-activity relationship

中图分类号: