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Citation: Wu Qian, Li Xianguo, Li Yan, Yang Ling. Study on the Structural Features and Binding Mode of Dihydroisoquinolines as BACE1 Inhibitors[J]. Chemistry, ;2016, 79(6): 509-515. shu

Study on the Structural Features and Binding Mode of Dihydroisoquinolines as BACE1 Inhibitors

Wu Qian ^1,2 ,
Li Xianguo ^1,, ,
Li Yan ³ ,
Yang Ling ⁴

1.
1. Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao 266100;
2.
2. Department of Chemical and Environmental Engineering, Weifang University, Weifang 261061;
3.
3. Department of Chemical Technology, Dalian University of Technology, Dalian 116024;
4.
4. Lab of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023

Corresponding author: Li Xianguo,
Received Date: 18 October 2015
Available Online: 18 February 2016
Fund Project:

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 Alzheimer's disease (AD). In this paper, 34 kinds of 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, R_ncv²=0.93, R_pre²=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.
- Dihydroisoquinoline,
- BACE1 inhibitors,
- CoMSIA,
- Molecular docking
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