通过碳碳双键连接的吲哚-2-酮与喹唑啉-4(3H)-酮杂合物的合成与抗肿瘤活性评价

doi:10.5246/jcps.2014.11.097

中国药学(英文版) ›› 2014, Vol. 23 ›› Issue (11): 765-771.DOI: 10.5246/jcps.2014.11.097

通过碳碳双键连接的吲哚-2-酮与喹唑啉-4(3H)-酮杂合物的合成与抗肿瘤活性评价

史博颖^1,3, 张晶晶¹, 曹胜利^1*, 高曼¹, 丁盼盼¹, 李中峰¹, 廖蓟², 许兴智^2*

1. 首都师范大学化学系, 北京 100048
2. DNA损伤应答北京市重点实验室; 首都师范大学生命科学学院, 北京 100048
3. 国家知识产权局专利局专利审查协作北京中心, 北京 100081

收稿日期:2014-06-10 修回日期:2014-07-26 出版日期:2014-11-24 发布日期:2014-08-01
通讯作者: Tel.: 86-10-68902974, 86-10-68902240
基金资助:
National Natural Science Foundation of China (Grant No. 20972099, 31130017), Beijing Municipal Commission of Education (Grant No. KZ201210028035), Scientific Research Base Development Program of the Beijing Municipal Commission of Education, and the 973 Project (Grant No. 2013CB911000).

Synthesis and cytotoxic evaluation of hybrids of indolin-2-one and quinazoline-4(3H)-one linked via carbon-carbon double bond

Boying Shi^1,3, Jingjing Zhang¹, Shengli Cao^1*, Man Gao¹, Panpan Ding¹, Zhongfeng Li¹, Ji Liao², Xingzhi Xu^2*

1. Department of Chemistry, Capital Normal University, Beijing 100048, China
2. Beijing Key Laboratory of DNA Damage Response; College of Life Science, Capital Normal University, Beijing 100048, China
3. Patent Examination Cooperation Center of the Patent Office, SIPO, Beijing 100081, China

Received:2014-06-10 Revised:2014-07-26 Online:2014-11-24 Published:2014-08-01
Contact: Tel.: 86-10-68902974, 86-10-68902240
Supported by:
National Natural Science Foundation of China (Grant No. 20972099, 31130017), Beijing Municipal Commission of Education (Grant No. KZ201210028035), Scientific Research Base Development Program of the Beijing Municipal Commission of Education, and the 973 Project (Grant No. 2013CB911000).

摘要/Abstract

摘要：

通过2-甲基-4-氧代喹唑啉-6-甲醛与不同的吲哚-2-酮的缩合反应, 制备了一系列吲哚-2-酮与喹唑啉-4(3H)-酮的杂合物5a-j。MTT法测试结果表明, 只有化合物5e对人肿瘤细胞A549、MCF-7、HeLa、HT-29 和HCT-116表现出一定的细胞毒活性, 50 µM浓度下的抑制率为32.0%-62.3%。

关键词: 吲哚-2-酮, 喹唑啉-4(3H)-酮, 细胞毒活性

Abstract:

A novel series of compounds combining indolin-2-one and quinazolin-4(3H)-one moietyvia a carbon-carbon double bond were synthesized by aldol-condensation of 2-methylquinazolin-4(3H)-one-6-carbaldehyde with various indolin-2-ones. The synthesized compounds were evaluated for their cytotoxic activity against five human cancer cell lines, namely, A549, MCF-7, HeLa, HT-29 and HCT-116. We found that compound 5e with two bromine atoms at the 5- and 7-positions of the indolin-2-one ring was most potent, which inhibited proliferation of five cancer cell lines in the range of32.0%–62.3% at a concentration of 50 µM. Our results further indicate that the connection of 5,7-dibromoindolin-2-one and 2-methylquinazolin-4(3H)-one moiety witha carbon-carbon double bondis essential for compound 5e to exert cytotoxicity.

Key words: Indolin-2-one, Quinazolin-4(3H)-one, Cytotoxic activity

中图分类号:

R916.4

Supporting:

史博颖, 张晶晶, 曹胜利, 高曼, 丁盼盼, 李中峰, 廖蓟, 许兴智. 通过碳碳双键连接的吲哚-2-酮与喹唑啉-4(3H)-酮杂合物的合成与抗肿瘤活性评价[J]. 中国药学(英文版), 2014, 23(11): 765-771.

Boying Shi, Jingjing Zhang, Shengli Cao, Man Gao, Panpan Ding, Zhongfeng Li, Ji Liao, Xingzhi Xu. Synthesis and cytotoxic evaluation of hybrids of indolin-2-one and quinazoline-4(3H)-one linked via carbon-carbon double bond[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(11): 765-771.

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通过碳碳双键连接的吲哚-2-酮与喹唑啉-4(3H)-酮杂合物的合成与抗肿瘤活性评价

Synthesis and cytotoxic evaluation of hybrids of indolin-2-one and quinazoline-4(3H)-one linked via carbon-carbon double bond

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