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

作者：Li, Kun; Li, Lei; Wang, Shuxiang; Li, Xiaojing; Ma, Tianyi; Liu, Dan^*; Jing, Yongkui^*; Zhao, Linxiang^*

来源：European Journal of Medicinal Chemistry, 2017, 126: 910-919.

DOI：10.1016/j.ejmech.2016.09.089

• Acetyl-11-keto-beta-boswellic acid
• Anti-proliferative activity
• Cyclin D1
• Cell cycle
• Pin1

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.

• 出版日期2017-1-27
• 单位沈阳药科大学