Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability. Issue 20 (15th October 2017)

• Record Type: Journal Article
• Authors: Li, Kun; Ma, Tianyi; Cai, Jingjing; Huang, Min; Guo, Hongye; Zhou, Di; Luan, Shenglin; Yang, Jinyu; Liu, Dan; Jing, Yongkui; Zhao, Linxiang
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 20(2017)
• Page Start: 5441
• Page End: 5451
• Publication Date: 2017-10-15
• Subjects: Pin1 inhibitors -- 18β-Glycyrrhetinic acid derivatives -- Anti-proliferative activity -- Cyclin D1; 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.2017.08.002
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Twenty-six conjugates of 18 β -glycyrrhetinic acid derivatives with 3-(1 H -benzo[ d ]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1 H -benzo[ d ]imidazol-2-yl)propanoic acid andGA . Compounds10a and12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80 μM and 3.52 μM, respectively. The enzyme inhibition ratio of nine compounds at 10 μM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C ofGA and suitable length of linker betweenGA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition.