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研究论文

新型吲哚-嘧啶联芳类化合物的设计、合成及抗肿瘤活性研究

张丹青a,b, 柳旭a,b, 庞晓静a,b, 刘宏民a,b,c, 张秋荣a,b,c   

  1. a 郑州大学药学院 郑州 450001;
    b 新药创制与药物安全性评价河南省协同创新中心 郑州 450001;
    c 教育部药物制备关键技术重点实验室 郑州 450001
  • 发布日期:2020-09-16
  • 通讯作者: 刘宏民, 张秋荣 E-mail:liuhm@zzu.edu.cn;zqr409@yeah.net
  • 基金资助:
    国家自然科学基金（No.U1904163）和蛋白关键研究项目（No.2018YFE0195100）资助项目和省部共建食管癌防治国家重点实验室资助的开放基金（K2020000X）

Design, Synthesis and Anticancer Activity Studies of Novel Indole-Pyrimidine Biaryl Derivatives

Dan-Qing Zhanga,b, Xu Liua,b, Xiao-Jing Panga,b, Hong-Min Liua,b,c, Qiu-Rong Zhanga,b,c   

  1. a School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001;
    b Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, Zhengzhou 450001) (c Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou 450001
  • Published:2020-09-16
  • Supported by:
    Project supported by Key Research Program of Proteins (No. 2018YFE0195100) and Openning fund from State Key Laboratory of Esophageal Cancer Prevention & Treatment (No. K2020000X)

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补充材料

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设计并合成了一系列新型的吲哚-嘧啶联芳类化合物，并评估了它们对LSD1的抑制活性和五种肿瘤细胞系（MGC-803，PC-3，EC-109，PC-12和MCF-7）的抗增殖活性。本论文探讨了22个新型吲哚-嘧啶联芳类骨架衍生物的主要构效关系。在这些化合物中，化合物6i展示出了较好的LSD1抑制活性（IC50=1.03µM），而化合物6c，6f和6k对PC-3细胞显示出较高的抗肿瘤活性。其中活性最强的化合物6k的IC50值为2.75µM，为开发更有效的抗肿瘤药物提供帮助。

关键词: 吲哚, 嘧啶, 联芳基, 抗肿瘤活性

A series of novel indole-pyrimidine biaryl derivatives were designed, synthesized and evaluated for inhibitory activity against LSD1 and antiproliferative activity against five selected cancer cell lines (MGC-803, PC-3, EC-109, PC-12 and MCF-7). The priliminary structure-activity relationship (SAR) for this indole-pyrimidine biaryl scaffold is explored in this report with evaluation of 22 variants of the structural class. Among these analogues, compound 6i exhibited the potential inhibitory activity against LSD1 (IC50=1.03 µM), compounds 6c, 6f and 6k showed the potential inhibitory activity aginst PC-3 cells. Especially, compound 6k exhibited the best antitumor activity (IC50=2.75 µM), which was served as bioactive fragment and hit compound for developing more potent antitumor agents.

Key words: Indole, Pyrimidine, Biaryl, Antitumor