Design, Synthesis and Biological Activities of N-(Furan-2-ylmethyl)-1H-indole-3-carboxamide Derivatives as Epidemal Growth Factor Receptor Inhibitors and Anticancer Agents

doi:10.1007/s40242-017-7041-x

Chemical Research in Chinese Universities ›› 2017, Vol. 33 ›› Issue (3): 365-372.doi: 10.1007/s40242-017-7041-x

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Design, Synthesis and Biological Activities of N-(Furan-2-ylmethyl)-1H-indole-3-carboxamide Derivatives as Epidemal Growth Factor Receptor Inhibitors and Anticancer Agents

ZHANG Lan¹, DENG Xinshan¹, WU Jiaofeng¹, MENG Guangpeng¹, LIU Congchong¹, CHEN Guzhou¹, ZHAO Qingchun², HU Chun¹

1. Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
2. Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang 110016, P. R. China

Received:2017-02-03 Revised:2017-04-17 Online:2017-06-01 Published:2017-04-24
Contact: HU Chun,E-mail:chunhu@syphu.edu.cn E-mail:chunhu@syphu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(No.21342006) and the Program for the Innovative Research Team of the Ministry of Education of China(No.IRT_14R36).

Abstract

Abstract:

A series of N-(furan-2-ylmethyl)-1H-indole-3-carboxamide derivatives(6a-6p) was designed and synthesized for developing novel indole scaffolds as anticancer agents targeting the epidemal growth factor receptor (EGFR), and the cytotoxic activities of the target compounds were evaluated against three EGFR high-expressed cancer cell lines[human lung adenocarcinoma cell line(A549), Henrietta Lacks strain of cancer cell line(HeLa) and human colorectal cancer cell line(SW480)], one EGFR low-expressed cell line(human liver cancer cell line, HepG2) and one human liver normal cell line(HL7702) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Some target compounds exhibited potent anticancer activities against A549, HeLa, SW480 and weak activities on HepG2, which signifies that the target compounds are likely to be EGFR inhibitors as expected. And they showed weak cytotoxic effects on HL7702, which implies the target compounds are probably to be of low toxicity against normal cells. Among them, the target compound 1-ethyl-N-(furan-2-ylmethyl)-5-{2-{[2-(2-methoxy-phenoxy)ethyl]amino}-2-oxoethoxy}-2-methyl-1H-indole-3-carboxamide(6p) with 2-{[2-(2-methoxyphenoxy)ethyl]-amino}-2-oxoethoxy group at the C5 position of the N-(furan-2-ylmethyl)-1H-indole-3-carboxamide scaffold exhibited the most potent anticancer activity. Also the binding interaction of the target compound 6p with EGFR was explored by molecular docking. Conclusively, the novel indole scaffold may be beneficial to investigate new anticancer agents for targeting the EGFR.

Key words: Anticancer activity, Epidemal growth factor receptor(EGFR) inhibitor, N-(Furan-2-ylmethyl)-1H-indole-3-carboxamide derivative

ZHANG Lan, DENG Xinshan, WU Jiaofeng, MENG Guangpeng, LIU Congchong, CHEN Guzhou, ZHAO Qingchun, HU Chun. Design, Synthesis and Biological Activities of N-(Furan-2-ylmethyl)-1H-indole-3-carboxamide Derivatives as Epidemal Growth Factor Receptor Inhibitors and Anticancer Agents[J]. Chemical Research in Chinese Universities, 2017, 33(3): 365-372.

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Design, Synthesis and Biological Activities of N-(Furan-2-ylmethyl)-1H-indole-3-carboxamide Derivatives as Epidemal Growth Factor Receptor Inhibitors and Anticancer Agents

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