高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

苯并γ-吡喃酮类PDE10A抑制剂的设计、合成及初步生物活性研究

吴伟俊1，何家静1，吴俊鹏1，蓝坤燕1，吴峥1,2   

  1. 1. 广西医科大学药学院 2. 广西医科大学广西生物活性分子研究与评价重点实验室

  • 收稿日期:2026-04-17 修回日期:2026-07-06 出版日期:2026-07-12 发布日期:2026-07-12
  • 通讯作者: 吴峥 E-mail:wuzheng@gxmu.edu.cn
  • 基金资助:
    国家自然科学基金（批准号：82260671）资助

Design, Synthesis and Preliminary Biological Evaluation of Chromone-Based PDE10A Inhibitors

WU Weijun1，HE Jiajing1，WU Junpeng1，LAN Kunyan1，WU Zheng1,2   

  1. 1. College of Pharmacy, Guangxi Medical University
    2. Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University
  • Received:2026-04-17 Revised:2026-07-06 Online:2026-07-12 Published:2026-07-12
  • Supported by:
    Supported by the National Natural Foundation of China (No.82260671)

PDF (PC)

补充材料

1

摘要： 基于PDE10A蛋白结构及其现有抑制剂相互作用模式的综合分析，采用拼合原理，设计合成了10个未经文献报道的PDE10A抑制剂. 活性测试结果显示，除化合物A4和A5外，其余化合物均表现出不同程度的抑制活性 (IC50=38.83~98.83 nmol/L). 挑选活性最好的化合物A1、A2和A9进行分子对接，发现它们均能嵌入PDE10A蛋白PHE729与ILE692/PHE696形成的疏水夹层中，通过π-π堆积和氢键发挥抑制作用. ADMET预测结果显示，这3个化合物具有良好的肠道吸收性、低血脑屏障透过率及较低的毒性，具备进一步开发为先导化合物的潜力.

关键词: 苯并γ-吡喃酮, PDE10A抑制剂, 合成, 分子对接, ADMET

Abstract: Based on the comprehensive analysis of the PDE10A protein structure and the interaction patterns of existing inhibitors, using the hybrid principle, ten new PDE10A inhibitors that have not been reported in the literature were designed and synthesized. The activity test results showed that except for compounds A4 and A5, the remaining compounds all exhibited varying degrees of inhibitory activity (IC50= 38.83~98.83 nmol/L). The most active compounds A1, A2, and A9 were selected for molecular docking, and it was found that they could all insert into the hydrophobic layer formed by PHE729 and ILE692/PHE696 in the PDE10A protein, exerting inhibitory effects through π-π stacking and hydrogen bonds. The ADMET prediction results indicated that these three compounds had good intestinal absorption properties, low blood-brain barrier permeability, and low toxicity, and had the potential to be further developed as lead compounds.

Key words: Chromone; PDE10A inhibitor, Synthesis, Molecular docking, ADMET

中图分类号: 

TrendMD: