Discovery of Novel Tricyclic 5H-Pyridazino[4,5-b]indoles as Potent Antitumor Agents: Design, Synthesis and Biological Evaluation

doi:10.1007/s40242-015-4435-5

高等学校化学研究 ›› 2015, Vol. 31 ›› Issue (3): 372-380.doi: 10.1007/s40242-015-4435-5

Discovery of Novel Tricyclic 5H-Pyridazino[4,5-b]indoles as Potent Antitumor Agents: Design, Synthesis and Biological Evaluation

ZHAI Xin, WANG Limei, SHI Jiyue, GONG Ping

Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

收稿日期:2014-11-19 修回日期:2014-12-04 出版日期:2015-06-01 发布日期:2014-12-22
通讯作者: GONG Ping E-mail:gongpinggp@126.com
基金资助:
Supported by the National Natural Science Foundation of China(No.81273357) and the Liaoning Baiqianwan Talents Program, China(No.2013921042).

Discovery of Novel Tricyclic 5H-Pyridazino[4,5-b]indoles as Potent Antitumor Agents: Design, Synthesis and Biological Evaluation

ZHAI Xin, WANG Limei, SHI Jiyue, GONG Ping

Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

Received:2014-11-19 Revised:2014-12-04 Online:2015-06-01 Published:2014-12-22
Contact: GONG Ping E-mail:gongpinggp@126.com
Supported by:
Supported by the National Natural Science Foundation of China(No.81273357) and the Liaoning Baiqianwan Talents Program, China(No.2013921042).

摘要/Abstract

摘要：

A novel series of 5H-pyridazino[4,5-b]indoles(L-01-L-32) was synthesized and characterized by means of ¹H NMR, MS and elemental analysis. The cytotoxicity of the target compounds against Bel-7402 and HT-1080 cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. Most of them exhibited moderate to excellent cytotoxicity, and six compounds(L-04, L-06, L-18, L-20, L-21 and L-23) possessed dramatically increased cytotoxicity superior to Gefitinib. Of these initial hits, compound L-21 displayed remarkable cytotoxicity against the tested cell lines with half maximal inhibitory concentration(IC₅₀) values of 4.6 and 2.1 μmol/L, respectively, which was 13.9- to 25.6-fold more potent than positive control.

关键词: 1-Anilino-5H-pyridazino[4,5-b]indole, EGFR inhibitor, Cytotoxicity

Abstract:

Key words: 1-Anilino-5H-pyridazino[4,5-b]indole, EGFR inhibitor, Cytotoxicity

ZHAI Xin, WANG Limei, SHI Jiyue, GONG Ping. Discovery of Novel Tricyclic 5H-Pyridazino[4,5-b]indoles as Potent Antitumor Agents: Design, Synthesis and Biological Evaluation[J]. 高等学校化学研究, 2015, 31(3): 372-380.

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Discovery of Novel Tricyclic 5H-Pyridazino[4,5-b]indoles as Potent Antitumor Agents: Design, Synthesis and Biological Evaluation

Discovery of Novel Tricyclic 5H-Pyridazino[4,5-b]indoles as Potent Antitumor Agents: Design, Synthesis and Biological Evaluation

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