2. Academic Validation
  3. Design and synthesis of indoline thiohydantoin derivatives based on enzalutamide as antiproliferative agents against prostate cancer

Design and synthesis of indoline thiohydantoin derivatives based on enzalutamide as antiproliferative agents against prostate cancer

  • Eur J Med Chem. 2017 Jan 5:125:1002-1022. doi: 10.1016/j.ejmech.2016.10.049.
Minzan Zuo 1,  Xi Xu 1,  Zhouling Xie 1,  Raoling Ge 1,  Ziyu Zhang 1,  Zhiyu Li 2,  Jinlei Bian 1
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 2 Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: zhiyuli@cpu.edu.cn.
PMID: 27810589 DOI: 10.1016/j.ejmech.2016.10.049
Abstract

A novel scaffold of indoline thiohydantoin was discovered as potent Androgen Receptor (AR) antagonist through rational drug designation. Several compounds showed good biological profiles in AR binding and higher selective toxicity than enzalutamide toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient). In addition, the docking studies supported the rationalization of the biological evaluation. Among these compounds, the representative compound 48c exhibited the strongest inhibitory effect on LNCaP growth and also acted as a competitive AR antagonist. Further preliminary mechanism study confirmed that 48c exerted its AR antagonistic activity through impairing AR nuclear translocation. All these results indicated that the novel scaffold compounds demonstrated AR antagonistic behavior and promising candidates for future development were identified.

Keywords

Androgen receptor; Antagonist; Indoline thiohydantoin derivatives; Prostate cancer.

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