2. Academic Validation
  3. Design, synthesis and biological evaluation of novel thiohydantoin derivatives as potent androgen receptor antagonists for the treatment of prostate cancer

Design, synthesis and biological evaluation of novel thiohydantoin derivatives as potent androgen receptor antagonists for the treatment of prostate cancer

  • Bioorg Med Chem. 2021 Feb 1:31:115953. doi: 10.1016/j.bmc.2020.115953.
Ao Wang 1,  Yawan Wang 2,  Xin Meng 3,  Yushe Yang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China; School of Pharmacy, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, PR China.
  • 2 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, PR China.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
  • 4 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China; School of Pharmacy, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, PR China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, PR China. Electronic address: ysyang@simm.ac.cn.
PMID: 33388655 DOI: 10.1016/j.bmc.2020.115953
Abstract

Prostate Cancer (PC) is the most common malignancy in men worldwide. Here, two series of novel thiohydantoin derivatives of enzalutamide as potent Androgen Receptor (AR) antagonists were designed and synthesized. Among them, compound 31c was identified as an AR antagonist which is 2.3-fold more potent than enzalutamide. Molecular docking studies were performed to explain the improved potency of 31c at AR. In cell proliferation assays, 31c exhibited similar anti-proliferative activities with enzalutamide against hormone sensitive LNCaP cells and AR-overexpressing LNCaP/AR cells. These data indicate that 31c can be a good lead compound for further structure optimization for the treatment of prostate Cancer.

Keywords

Androgen receptor; Androgen receptor antagonists; Novel thiohydantoin derivatives; Prostate cancer.

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