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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
1. [1]
  [1] R Vassar, D M Kovacs, R Yan et al. J. Neurosci., 2009, 29(41):12787~12794.
2. [2]
  [2] L McConlogue, M Buttini, J P Anderson et al. J. Biol. Chem., 2007, 282:26326~26334.
3. [3]
  [3] A Burns, S Iliffe. Alzheimer's Disease. BMJ, 2009, 338:b158.
4. [4]
  [4] R Vassar, B D Bennett, B S Abu-Khan et al. Science, 1999, 286:735~741.
5. [5]
  [5] L McConlogue, M Buttini, J P Anderson et al. J. Biol. Chem., 2007, 282:26326~26334.
6. [6]
  [6] Y Luo, B Bolon, S Kahn et al. Nat. Neurosci., 2001, 4:231~232.
7. [7]
  [7] A K Ghosh, H L Osswald. Chem. Soc. Rev., 2014, 43:6765~6813.
8. [8]
  [8] J Yuan, S Venkatraman, Y Zheng et al. J. Med. Chem., 2013, 56:4156~4180.
9. [9]
  [9] L Zhang, T Liu, X Wang et al. Biosystems, 2014, 115:13~22.
10. [10]
  [10] S P Wei, Z Q Ji, H X Zhang et al. J. Mol. Model., 2011, 17:681~693.
11. [11]
  [11] J L Liu, F F Wang, Z Ma et al. Int. J. Mol. Sci., 2011, 12(2):946~970.
12. [12]
  [12] S Bowers, Y Xu, S Yuan et al. Bioorg. Med. Chem. Lett., 2013, 23(7):2181~2186.
13. [13]
  [13] Y Xu, S Yuan, S Bowers et al. Bioorg. Med. Chem. Lett., 2013, 23(10):3075~3080
14. [14]
  [14] J Gasteiger, M Marsili. Tetrahedron, 1980, 36:3219~3228.
15. [15]
  [15] M Clark, R D Cramer, N Van Opdenbosch. J. Comput. Chem., 1989, 10:982~1012.
16. [16]
  [16] M Clark, R D Cramer. Quant. Struct-Act. Rel., 1993, 12:137~145.
17. [17]
  [17] M L Verdonk, J C Cole, M J Hartshorn et al. Proteins, 2003, 52:609~623.
18. [18]
  [18] J Z Chen, X W Han, Q Liu et al. J. Med. Chem., 2006, 49:625~636.
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