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

Bioorg Med Chem. 2016 Apr 15;24(8):1889-97. doi: 10.1016/j.bmc.2016.03.016.

Kun Li ¹, Ying Li ², Di Zhou ¹, Yinbo Fan ¹, Hongye Guo ¹, Tianyi Ma ¹, Jiachen Wen ¹, Dan Liu ³, Linxiang Zhao ⁴

Affiliations

1 Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
2 School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
3 Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: sammyld@163.com.
4 Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: linxiang.zhao@vip.sina.com.

PMID: 26979485 DOI: 10.1016/j.bmc.2016.03.016

Abstract

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 GI50 values of 2.60, 2.81 and 1.29 μM, 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.

Keywords

Anti-proliferative activity; Pim-1 kinase inhibitor; Prostate cancer; Quinoline derivatives.

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