| 吴倩,高庆平,刘莉,李丹,李燕,杨凌.化学通报,2018,81(8):745-752. |
| 氨基恶唑啉呫吨类BACE1抑制剂的特征结构与作用机制 |
| The structural features and interaction mechanism exploration of aminooxazoline xanthenes as BACE1 inhibitors |
| 投稿时间：2018-01-27 修订日期：2018-04-18 |
| DOI： |
| 中文关键词: 氨基恶唑啉呫吨BACE1抑制剂 特征结构 分子对接 作用机制 |
| 英文关键词:Aminooxazoline xanthene BACE1 inhibitors, Structural features, Molecular docking, Interaction mechanism |
| 基金项目: |
|
| 摘要点击次数: 2246 |
| 全文下载次数: 0 |
| 中文摘要: |
| β-分泌酶(BACE1)是治疗阿尔兹海默症(AD)的潜在靶点,BACE1抑制剂的开发已成为治疗AD的重要方向。本文运用比较分子相似性指数(CoMSIA)和分子对接法对66个氨基恶唑啉呫吨类BACE1抑制剂进行模拟分析,建立了可靠的构效关系预测模型(Q2=0.86, Rncv2=0.97, Rpre2=0.88),揭示了影响分子抑制活性的重要特征结构信息,发现抑制剂通过与BACE1之间形成的氢键作用和π-π堆积作用占据了分泌酶的S3、S1和S2"三个活性位点。实验所得模型和信息为后续新型高效BACE1抑制剂的结构优化和改造提供了重要的理论指导。 |
| 英文摘要: |
| β-secretase (BACE1) is a potent target for Alzheimer"s disease (AD). Inhibition of BACE1 has gained considerable attention as a potential disease-modifying treatment of AD. In this study, 66 aminooxazoline xanthene-based BACE1 inhibitors were simulated by comparative molecular similarity index (CoMSIA) and molecular docking methods. A reliable prediction model of structure-activity relationship (Q2= 0.86, Rncv2=0.97, Rpre2= 0.88) was constructed, revealing the important structural features information that influences the inhibitory activity of the molecules. Moreover, it was found that the inhibitor occupies S3, S1 and S2" active sites of target through hydrogen bonding and π-π stacking interactions formed with BACE1. The model and information deduced from this in silico analysis provide important theoretical guidance for the structural optimization and modification of new and efficient BACE1 inhibitors. |
| 查看全文 查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|