新型硫代海因衍生物的设计、合成及雄激素受体拮抗活性评价：用于前列腺癌治疗的潜在药物。
Design, synthesis and biological evaluation of novel thiohydantoin derivatives as potent androgen receptor antagonists for the treatment of prostate cancer.
机构信息
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.
出版信息
Bioorg Med Chem. 2021 Feb 1;31:115953. doi: 10.1016/j.bmc.2020.115953. Epub 2020 Dec 16.
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.
前列腺癌（PC）是全球男性最常见的恶性肿瘤。在这里，我们设计并合成了两种新型的恩扎鲁胺硫代海因衍生物，它们都是有效的雄激素受体（AR）拮抗剂。其中，化合物 31c 被鉴定为一种 AR 拮抗剂，其对 AR 的抑制活性比恩扎鲁胺强 2.3 倍。通过分子对接研究解释了 31c 在 AR 上增强活性的原因。在细胞增殖实验中，31c 对激素敏感的 LNCaP 细胞和 AR 过表达的 LNCaP/AR 细胞的增殖抑制活性与恩扎鲁胺相似。这些数据表明，31c 可以作为一个良好的先导化合物，进一步进行结构优化，用于治疗前列腺癌。
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