Virtual screen of effective AChE inhibitory constituents from Radix Glycyrrhizae based on pharmacophore and molecular docking

LIU Guang-xin1 ZHAO Ze-feng2 XIE Jing2 SANG Jie1 LIANG Ye-fei1 QIAN Ming-cheng3 LI Cui-qin1

(1.Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi Province 710062)
(2.Biomedicine Key Laboratory of Shaanxi Province, Northwest University, Xi’an, Shaanxi Province 710069)
(3.School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164)

【Abstract】This research is to predict anti-Alzheimer’s disease active constituents on the target of acetylcholinesterase (AChE) from Radix Glycyrrhizae with the help of pharmacophore and molecular docking. AChE ligand-based pharmacophore model was set up and the molecular library of the constituents from Radix Glycyrrhizae was established by collecting literature. Then the constituents from Radix Glycyrrhizae were screened for the potential AChE inhibitory potency in silico through matching with the best pharmacophore model. The flexible docking was used to evaluate the interactions between the compounds screened from pharmacophore model and AChE protein (PDB ID: 4EY7). The interactions were expressed including but not limited to CDOCKER interaction energy, hydrogen bonds and non-bonding interactions. The molecular library of Radix Glycyrrhizae contained 44 chemical constituents. As for the pharmacophore model, six kinds of potential AChE inhibitory constituents from Radix Glycyrrhizae were considered to be promising compounds according to the results of searching 3D database of pharmacophore model. The molecular docking was carried out and the interaction patterns were given to show the detailed interactions. The compounds screened from the pharmacophore model were consistent with the existing studies to some degree, indicating that the virtual screen protocols of AChE inhibitory constituents from Radix Glycyrrhizae based on pharmacophore and molecular docking were reliable.

【Keywords】 Radix Glycyrrhizae; AChE inhibitor; anti-dementia; pharmacophore; molecular docking;

【DOI】

【Funds】 National Key Research & Development Project (2018YFC1706500)

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(Translated by FU LJ)

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This Article

ISSN:1001-5302

CN:11-2272/R

Vol 45, No. 10, Pages 2431-2438

May 2020

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Article Outline

Abstract

  • 1 Materials and methods
  • 2 Results
  • 3 Discussion
  • References