| 卢鹏辉,胡晓琳,周子坤,等.雄激素受体N末端结构域拮抗剂的设计、合成及活性评价[J].中国海洋药物,2025,44(6):70-74. |
| 雄激素受体N末端结构域拮抗剂的设计、合成及活性评价 |
| Design, synthesis and bioactivity evaluation of androgen receptor N-terminal domain antagonists |
| 投稿时间：2024-03-27 修订日期：2024-04-29 |
| DOI：10.13400/j.cnki.cjmd.2025.06.006 |
| 中文关键词: 雄激素受体 共价结合 拮抗剂 前列腺癌 |
| English Keywords:androgen receptor covalent binding antagonist prostate cancer |
| Fund Project: |
|
| 摘要点击次数: 309 |
| 全文下载次数: 1 |
| 中文摘要: |
| 目的 以共价结合于AR-NTD的海洋天然产物为灵感,设计合成潜在的新型AR-NTD共价拮抗剂。方法 以芳基吡唑-1-基丙酰胺类化合物为先导,通过引入共价弹头,合成衍生物并进行前列腺癌细胞增殖抑制活性测试。结果 合成共计4个芳基吡唑-1-基丙酰胺类衍生物A1~A4,在22Rv1细胞中,化合物A1~A4均表现出一定的增殖抑制效果。A1、A3的活性优于阳性对照分子26a,其中A3的活性比阳性对照分子26a提升2倍,IC50为2.04 μmol/L。 |
| English Summary: |
| Objective Developing potential new covalent antagonists for AR-NTD inspired by marine natural products that are covalently bound to NTD. Methods The derivatives were created by adding covalent warheads to aryl pyrazol-1-yl propanamide scaffold and the proliferation inhibition activity of prostate cancer cells was tested. Results A total of four aryl pyrazole-1-propionamide derivatives A1-A4 were synthesized. In 22Rv1 cells, compounds A1-A4 exhibited a certain proliferation inhibition effect. Both A1 and A3 were superior to the control molecule 26a, and the activity of A3 was 2 times higher than that of 26a, with IC50 of 2.04 μmol/L. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
|
| 关闭 |