Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors

Citation: Jun-Peng Zhang, Jie Huang, Chao Liu, Xu-Fang Lu, Bao-Xiang Wu, Li Zhao, Na Lu, Qing-Long Guo, Zhi-Yu Li, Cheng Jiang. Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors[J]. Chinese Chemical Letters, 2014, 25(7): 1025-1028. doi: 10.1016/j.cclet.2014.05.048 shu

Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors

通讯作者: Zhi-Yu Li,
Cheng Jiang,

基金项目:
This work was supported by the National Natural Science Foundation of China (No. 21072232) (No. 21072232)

the Fundamental Research Funds for the Central Universities (No. JKZ2011002) (No. JKZ2011002)

Innovative Research Team in University (No. PCSIRT-IRT1193) (No. PCSIRT-IRT1193)

摘要: A series of new 3-benzoheterocyclic substituted pyridopyrimidines were designed and synthesized. Structures of the compounds were determined by IR, ¹H NMR, and elemental analyses. The antiproliferation activity of 13 novel compounds was evaluated in A549, HL-60, BGC-823 and SMMC-7721 cell lines. Compounds 3, 5, 7, 8, 9, 10 showed potent inhibitory activity against the four tested cancer cell lines. These six compounds were examined for Top I inhibition at 100 mmol/L by measuring the relaxation of supercoiled DNA in plasmid pBR322. Most of the tested compounds inhibited the enzyme at this concentration. The most potent compound 9 was as potent as camptothecin.

关键词:

English

Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors

1.
a Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;
2.
b Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;
3.
c Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China;
4.
d Gansu Institute for Food and Drug Control, Lanzhou 730070, China

Corresponding author: Zhi-Yu Li, Cheng Jiang,

Received Date: 25 March 2014
Fund Project:

Abstract: A series of new 3-benzoheterocyclic substituted pyridopyrimidines were designed and synthesized. Structures of the compounds were determined by IR, ¹H NMR, and elemental analyses. The antiproliferation activity of 13 novel compounds was evaluated in A549, HL-60, BGC-823 and SMMC-7721 cell lines. Compounds 3, 5, 7, 8, 9, 10 showed potent inhibitory activity against the four tested cancer cell lines. These six compounds were examined for Top I inhibition at 100 mmol/L by measuring the relaxation of supercoiled DNA in plasmid pBR322. Most of the tested compounds inhibited the enzyme at this concentration. The most potent compound 9 was as potent as camptothecin.

Key words:

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Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors

通讯作者: Zhi-Yu Li,
Cheng Jiang,

English

Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors

Corresponding author: Zhi-Yu Li, Cheng Jiang,

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors

通讯作者: Zhi-Yu Li, Cheng Jiang,

English

Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors

Corresponding author: Zhi-Yu Li, Cheng Jiang,

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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