Synthesis and biological evaluation of quinoline derivatives as potential anti-prostate cancer agents and Pim-1 kinase inhibitors. Issue 8 (15th April 2016)

• Record Type: Journal Article
• Authors: Li, Kun; Li, Ying; Zhou, Di; Fan, Yinbo; Guo, Hongye; Ma, Tianyi; Wen, Jiachen; Liu, Dan; Zhao, Linxiang
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 8(2016)
• Page Start: 1889
• Page End: 1897
• Publication Date: 2016-04-15
• Subjects: Quinoline derivatives -- Anti-proliferative activity -- Pim-1 kinase inhibitor -- Prostate cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.03.016
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 and9g 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 that9g 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.