| 吴倩,李先国,李燕,杨凌.化学通报,2016,79(6):509-515. |
| 二氢异喹啉类BACE1抑制剂的特征结构及结合模式研究 |
| Study on the Structural Features and Binding Mode of Dihydroisoquinolines as BACE1 Inhibitors |
| 投稿时间：2015-10-18 修订日期：2015-11-23 |
| DOI： |
| 中文关键词: 二氢异喹啉 BACE1抑制剂 比较分子相似性指数法 分子对接 |
| 英文关键词:Dihydroisoquinoline, BACE1 inhibitors, CoMSIA, Molecular docking |
| 基金项目:(2014Z11)资助 |
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| 摘要点击次数: 2832 |
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| 中文摘要: |
| β-分泌酶(BACE1)是水解淀粉样前体蛋白生成β-淀粉样多肽的关键限速酶,近年来已成为治疗阿尔兹海默症的一个理想靶点。本文以34个二氢异喹啉类BACE1抑制剂为研究对象,采用比较分子相似性指数(CoMSIA)法定量研究其结构与生物活性间的构效关系,并建立可靠的3D-QSAR预测模型,运用分子对接法分析其与受体BACE1间的结合模式。结果显示,基于立体场、疏水场和氢键供体场建立的CoMSIA模型稳定性良好、预测能力强(Q2=0.47, Rncv2=0.93, Rpre2=0.95)。本研究所得模型和信息较好地解释了二氢异喹啉类BACE1抑制剂的结构特征及其与受体间的结合模式,为后续新型BACE1抑制剂的设计开发提供理论指导。 |
| 英文摘要: |
| β-secretase (BACE1) is responsible for the initial cleavage of transmembrane amyloid precursor protein that leads to the production of β-amyloid (Aβ) peptides in the brain, and is a prime target for AD. In this paper, 34 dihydroisoquinoline derivatives as BACE1 inhibitors were studied by three-dimensional quantitative structure-activity relationship and molecular docking methods. The resultant optimal comparative molecular similarity indices analysis (CoMSIA) model, constructed based on the steric, hydrophobic and hydrogen-bond donor fields, displays a strong predictability (Q2=0.47, Rncv2=0.93, Rpre2=0.95). This model and the derived information may help to provide better understanding of the structure features and binding mode of BACE1 inhibitors and to facilitate corresponding novel inhibitors’ design. |
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