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

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

  • Eur J Med Chem. 2017 Jan 27:126:910-919. doi: 10.1016/j.ejmech.2016.09.089.
Kun Li 1,  Lei Li 2,  Shuxiang Wang 1,  Xiaojing Li 1,  Tianyi Ma 1,  Dan Liu 3,  Yongkui Jing 4,  Linxiang Zhao 5
Affiliations

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 School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: yongkjing@yahoo.com.
  • 5 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: 27997878 DOI: 10.1016/j.ejmech.2016.09.089
Abstract

A series of novel acetyl-11-keto-β-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 μM) and LNCaP (IC50 = 0.27 μM) 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.

Keywords

Acetyl-11-keto-β-boswellic acid; Anti-proliferative activity; Cell cycle; Cyclin D1; Pin1.

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