Design, Synthesis and Pharmacological Evaluation of Novel 4-Phenoxyquinoline Derivatives as Potential Antitumor Agents

doi:10.1007/s40242-015-5166-3

Chemical Research in Chinese Universities ›› 2015, Vol. 31 ›› Issue (5): 746-755.doi: 10.1007/s40242-015-5166-3

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Design, Synthesis and Pharmacological Evaluation of Novel 4-Phenoxyquinoline Derivatives as Potential Antitumor Agents

HU Hao¹, JIANG Mingyan¹, XIE Lijun², HU Gang¹, ZHANG Cuirong¹, ZHANG Lixia¹, ZHOU Shunguang¹, ZHANG Meihui¹, GONG Ping¹

1. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
2. Fujian Institute of Microbiology, Fuzhou 350007, P. R. China

Received:2015-04-22 Revised:2015-07-06 Online:2015-10-01 Published:2015-07-22
Contact: ZHANG Meihui, E-mail: zhangmeihui2005@gmail.com; GONG Ping, E-mail: gongpinggp@126.com E-mail:zhangmeihui2005@gmail.com;gongpinggp@126.com
Supported by:
Supported by the Program for Liaoning Innovative Research Team in University, China(No.IRT1073).

Abstract

Abstract:

A series of novel 4-phenoxyquinoline derivatives containing 3-amino-2-cyano-acrylamide framework was designed and synthesized, and the in vitro cytotoxic activities of them against five cancer cell lines(HT-29, H460, A549, MKN-45, and U87MG) were evaluated. Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines as compared with Foretinib. The studies of their preliminary structure-activity relationships(SARs) indicate that the compounds containing methyl groups, especially methyl groups at 4-position of the phenyl ring(moiety B) are more effective. Among them, compound 36 shows the most potent antitumor activities with IC₅₀ values of 0.04, 0.09, 0.67, 0.39 and 1.10 μmol/L against HT-29, H460, A549, MKN-45 and U87MG cell lines, respectively.

Key words: 4-Phenoxyquinoline derivative, Cytotoxic activity, 3-Amino-2-cyano-acrylamide

HU Hao, JIANG Mingyan, XIE Lijun, HU Gang, ZHANG Cuirong, ZHANG Lixia, ZHOU Shunguang, ZHANG Meihui, GONG Ping. Design, Synthesis and Pharmacological Evaluation of Novel 4-Phenoxyquinoline Derivatives as Potential Antitumor Agents[J]. Chemical Research in Chinese Universities, 2015, 31(5): 746-755.

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Design, Synthesis and Pharmacological Evaluation of Novel 4-Phenoxyquinoline Derivatives as Potential Antitumor Agents

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