Design and synthesis of novel 2-substituted 11-keto-boswellic acid heterocyclic derivatives as anti-prostate cancer agents with Pin1 inhibition ability

被引：27
作者：
Li, Kun [1 ]
Li, Lei [2 ]
Wang, Shuxiang [1 ]
Li, Xiaojing [1 ]
Ma, Tianyi [1 ]
Liu, Dan [1 ]
Jing, Yongkui [2 ]
Zhao, Linxiang [1 ]
机构：
[1] Shenyang Pharmaceut Univ, Key Lab Struct Based Drugs Design Discovery Minis, Shenyang 110016, Peoples R China
[2] Shenyang Pharmaceut Univ Shenyang 110016, Sch Life Sci & Biopharmaceut, Shenyang, Peoples R China
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 126卷
基金：
中国国家自然科学基金;
关键词：
Acetyl-11-keto-beta-boswellic acid; Anti-proliferative activity; Cyclin D1; Cell cycle; Pin1; NF-KAPPA-B; BOSWELLIC ACIDS; 11-KETO-BETA-BOSWELLIC ACID; INDUCE APOPTOSIS; HL-60; CELLS; GROWTH; PATHWAY; DEATH; TRITERPENOIDS; NOXA;
D O I：
10.1016/j.ejmech.2016.09.089
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of novel acetyl-11-keto-beta-boswellic acid (AKBA) derivatives with a different electron-withdrawing group on ring A and a nitrogen heterocycle at C-24 were designed and synthesized. These semi-synthetic compounds showed improved anti-proliferative activity against prostate cancer cells over AKBA. Compound 8f bearing 2-cyano-3,11-dioxo moiety and piperazine was the most potent to inhibit growth of prostate cancer PC-3 (IC50 = 0.04 mu M) and LNCaP (IC50 = 0.27 mu M) cell lines. 8f caused cell cycle arrest in G2/M and induced apoptosis. 8f decreased the protein levels of anti-apoptosis protein Mcl-1, c-FLIP and cell cycle regulating protein cyclin D1. 8f inhibited the activity of Pin1, a peptidyl-prolyl cis-trans isomerase to stabilize cyclin D1. 8f represented a compound with improved anti-proliferative effects for prostate cancer therapy working through new mechanisms. (C) 2016 Published by Elsevier Masson SAS.
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收藏
页码：910 / 919
页数：10
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