Synthesis and biological evaluation of quinoline derivatives as potential anti-prostate cancer agents and Pim-1 kinase inhibitors

被引：60

作者：

Li, Kun ^{[1
]}

Li, Ying ^{[2
]}

Zhou, Di ^{[1
]}

Fan, Yinbo ^{[1
]}

Guo, Hongye ^{[1
]}

Ma, Tianyi ^{[1
]}

Wen, Jiachen ^{[1
]}

Liu, Dan ^{[1
]}

Zhao, Linxiang ^{[1
]}

机构：

[1] Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drugs Design & Discovery, Shenyang 110016, Peoples R China

[2] Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Shenyang 110016, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2016年 / 24卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Quinoline derivatives; Anti-proliferative activity; Pim-1 kinase inhibitor; Prostate cancer; THERAPY; ARIPIPRAZOLE; DISCOVERY; DRUG;

D O I：

10.1016/j.bmc.2016.03.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this work, a series of quinoline derivatives were designed and synthesized as antitumor agents. Most quinolines showed potent anti-proliferative activity against human prostatic cancer PC-3 cell line. Among which, 9d, 9f and 9g were the most effective compounds with GI(50) values of 2.60, 2.81 and 1.29 mu M, respectively. Structure-activity relationship analysis indicated that the secondary amine linked quinoline and pyridine ring played an important role in the anti-proliferative effects. Mechanistic studies revealed that 9g was a potential Pim-1 kinase inhibitor with abilities of cell cycle arrest and apoptosis induction. Considering of the increased activity of Pim-1 in prostate cancer, such compounds have potential to be developed as anti-prostate cancer agents. (C) 2016 Published by Elsevier Ltd.

引用

页码：1889 / 1897

页数：9

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