Citation: Wu Qian, Gao Qingping, Liu Li, Li Dan, Li Yan, Yang Ling. The Structural Features and Interaction Mechanism Exploration of Aminooxazoline Xanthenes as BACE1 Inhibitors[J]. Chemistry, ;2018, 81(8): 745-752. shu

The Structural Features and Interaction Mechanism Exploration of Aminooxazoline Xanthenes as BACE1 Inhibitors

Wu Qian ^1, ,
Gao Qingping ² ,
Liu Li ¹ ,
Li Dan ¹ ,
Li Yan ³ ,
Yang Ling ⁴

1.
Department of Chemical and Environmental Engineering, Weifang University, Weifang 261061
2.
School of Chemical Engineering, Weifang Vocational College, Weifang 262737
3.
Department of Materials Science and Chemical Engineering, Dalian University of Technology, Dalian 116024
4.
Lab of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Graduate School of the Chinese Academy of Sciences, Dalian 116023

Received Date: 27 January 2018
Accepted Date: 7 May 2018

Figures(5)

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, R_ncv²=0.97, R_pre²=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.
- Aminooxazoline xanthene BACE1 inhibitors,
- Structural features,
- Molecular docking,
- Intera-ction mechanism
1. [1]
  M Citron. Nat. Rev. Drug Discov., 2010, 9:387~398.
2. [2]
  D J Selkoe, J Hardy. EMBO Mol. Med., 2016, 8(6):595~608.
3. [3]
  A K Ghosh, H L Osswald. Chem. Soc. Rev., 2014, 43:6765~6813.
4. [4]
  C E H Moussa. Expert Opin. Inv. Drug., 2017, 26(10):1131~1136.
5. [5]
  R Yan. Transl. Neurodegener., 2016, 5:13.
6. [6]
  H Huang, D S La, A C Cheng et al. J. Med. Chem., 2012, 55:9156~9169.
7. [7]
  O Epstein, M C Bryan, A C Cheng et al. J. Med. Chem., 2014, 57:9796~9810.
8. [8]
9. [9]
10. [10]
  M L Verdonk, J C Cole, M J Hartshorn et al. Proteins, 2003, 52:609~623.
11. [11]
  L Hong, G Koelsch, X Lin et al. Science, 2000, 290:150~153.
12. [12]
  D Van Der Spoel, E Lindahl, B Hess et al. J. Comput. Chem., 2005, 26:1701~1718.
13. [13]
  E Aghaee, J B Ghasemi, F Manouchehri et al. J. Mol. Model., 2014, 20:1~13.
14. [14]
  J Yuan, S Venkatraman, Y Zheng et al. J. Med. Chem., 2013, 56:4156~4180.
1. [1]
  Zhi Zhou , Yu-E Lian , Yuqing Li , Hui Gao , Wei Yi . New Insights into the Molecular Mechanism Behind Clinical Tragedies of “Cephalosporin with Alcohol”. University Chemistry, 2025, 40(3): 42-51. doi: 10.12461/PKU.DXHX202403104
2. [2]
  Tong Zhou , Liyi Xie , Chuyu Liu , Xiyan Zheng , Bao Li . Between Sobriety and Intoxication: The Fascinating Journey of Sauce-Flavored Latte. University Chemistry, 2024, 39(9): 55-58. doi: 10.12461/PKU.DXHX202312048
3. [3]
  Yanglin Jiang , Mingqing Chen , Min Liang , Yige Yao , Yan Zhang , Peng Wang , Jianping Zhang . Experimental and Theoretical Investigations of Solvent Polarity Effect on ESIPT Mechanism in 4′-N,N-diethylamino-3-hydroxybenzoflavone. Acta Physico-Chimica Sinica, 2025, 41(2): 2309027-0. doi: 10.3866/PKU.WHXB202309027
4. [4]
  Yuxin CHEN , Yanni LING , Yuqing YAO , Keyi WANG , Linna LI , Xin ZHANG , Qin WANG , Hongdao LI , Wenmin WANG . Construction, structures, and interaction with DNA of two Sm^Ⅲ₄ complexes. Chinese Journal of Inorganic Chemistry, 2025, 41(6): 1141-1150. doi: 10.11862/CJIC.20240258
5. [5]
  Wen-Bing Hu . Systematic Introduction of Polymer Chain Structures. University Chemistry, 2025, 40(4): 15-19. doi: 10.3866/PKU.DXHX202401014
6. [6]
  Jiaxun Wu , Mingde Li , Li Dang . The R eaction of Metal Selenium Complexes with Olefins as a Tutorial Case Study for Analyzing Molecular Orbital Interaction Modes. University Chemistry, 2025, 40(3): 108-115. doi: 10.12461/PKU.DXHX202405098
7. [7]
  Changqing MIAO , Fengjiao CHEN , Wenyu LI , Shujie WEI , Yuqing YAO , Keyi WANG , Ni WANG , Xiaoyan XIN , Ming FANG . Crystal structures, DNA action, and antibacterial activities of three tetranuclear lanthanide-based complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2455-2465. doi: 10.11862/CJIC.20240192
8. [8]
  Shuang Meng , Haixin Long , Zhou Zhou , Meizhu Rong . Inorganic Chemistry Curriculum Design and Implementation of Based on “Stepped-Task Driven + Multi-Dimensional Output” Model: A Case Study on Intermolecular Forces. University Chemistry, 2024, 39(3): 122-131. doi: 10.3866/PKU.DXHX202309008
9. [9]
  Yihui Song , Shangshang Qin , Kai Wu , Chengyun Jin , Bin Yu . 生物化学在高水平创新型药学人才培养中的交叉融合应用——以去甲基化酶LSD1抑制剂的活性评价为例. University Chemistry, 2025, 40(6): 341-352. doi: 10.12461/PKU.DXHX202406018
10. [10]
  Wenyan Dan , Weijie Li , Xiaogang Wang . The Technical Analysis of Visual Software ShelXle for Refinement of Small Molecular Crystal Structure. University Chemistry, 2024, 39(3): 63-69. doi: 10.3866/PKU.DXHX202302060
11. [11]
  Pei Li , Yuenan Zheng , Zhankai Liu , An-Hui Lu . Boron-Containing MFI Zeolite: Microstructure Control and Its Performance of Propane Oxidative Dehydrogenation. Acta Physico-Chimica Sinica, 2025, 41(4): 2406012-0. doi: 10.3866/PKU.WHXB202406012
12. [12]
  Hui Wang , Abdelkader Labidi , Menghan Ren , Feroz Shaik , Chuanyi Wang . Recent Progress of Microstructure-Regulated g-C₃N₄ in Photocatalytic NO Conversion: The Pivotal Roles of Adsorption/Activation Sites. Acta Physico-Chimica Sinica, 2025, 41(5): 100039-0. doi: 10.1016/j.actphy.2024.100039
13. [13]
  Xinyu ZENG , Guhua TANG , Jianming OUYANG . Inhibitory effect of Desmodium styracifolium polysaccharides with different content of carboxyl groups on the growth, aggregation and cell adhesion of calcium oxalate crystals. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1563-1576. doi: 10.11862/CJIC.20230374
14. [14]
  Wenliang Wang , Weina Wang , Sufan Wang , Tian Sheng , Tao Zhou , Nan Wei . “Schrödinger Equation – Approximate Models – Core Concepts – Simple Applications”: Constructing a Logical Framework and Knowledge Graph of Atom and Molecule Structures. University Chemistry, 2024, 39(8): 338-343. doi: 10.3866/PKU.DXHX202312084
15. [15]
  Yaping Li , Sai An , Aiqing Cao , Shilong Li , Ming Lei . The Application of Molecular Simulation Software in Structural Chemistry Education: First-Principles Calculation of NiFe Layered Double Hydroxide. University Chemistry, 2025, 40(3): 160-170. doi: 10.12461/PKU.DXHX202405185
16. [16]
  Yuan Chun , Yongmei Liu , Fuping Tian , Hong Yuan , Shu'e Song , Wanchun Zhu , Yunchao Li , Zhongyun Wu , Xiaokui Wang , Yunshan Bai , Li Wang , Jianrong Zhang , Shuyong Zhang . Suggestions on Operating Specifications of Physical Chemistry Experiment: Measurement of Colloidal and Surface Chemical Properties, Molecular Structure and Properties. University Chemistry, 2025, 40(5): 178-188. doi: 10.12461/PKU.DXHX202503053
17. [17]
  Manman Jin , Zhiguo Lv , Qingtao Niu . Teaching Reformation and Case Study for “Chemical Process Development and Design” Based on “Just-in-Time” Dynamic and Accurate Matching Industrial Needs. University Chemistry, 2024, 39(11): 108-116. doi: 10.12461/PKU.DXHX202403030
18. [18]
  Zhonghua Xi , Xuanfeng Kong , Jinyue Yang , Bin Liu , Tingyu Zhu , Hui Zhang , Wenwei Zhang . Construction of Public Teaching Instrument Platform and Exploration of Opening Mechanism. University Chemistry, 2024, 39(7): 200-206. doi: 10.12461/PKU.DXHX202405123
19. [19]
  Shuhui Li , Rongxiuyuan Huang , Yingming Pan . Electrochemical Synthesis of 2,5-Diphenyl-1,3,4-Oxadiazole: A Recommended Comprehensive Organic Chemistry Experiment. University Chemistry, 2025, 40(5): 357-365. doi: 10.12461/PKU.DXHX202407028
20. [20]
  Yonghui ZHOU , Rujun HUANG , Dongchao YAO , Aiwei ZHANG , Yuhang SUN , Zhujun CHEN , Baisong ZHU , Youxuan ZHENG . Synthesis and photoelectric properties of fluorescence materials with electron donor-acceptor structures based on quinoxaline and pyridinopyrazine, carbazole, and diphenylamine derivatives. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 701-712. doi: 10.11862/CJIC.20230373

Get Citation

PDF

XML

Metrics

PDF Downloads(11)
Abstract views(1995)
HTML views(873)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142