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;


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

Download this article

(Translated by FU LJ)


    [1] XIAO Q L. A new method to characterize the kinetics of cholinesterases inhibition [D]. Guangzhou: South China University of Technology, 2018 (in Chinese).

    [2] XIE W, STRIBLEY J A, CHATONNET A, et al. Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase [J]. J Pharmacol Exp Ther, 2000, 293 (3): 896.

    [3] WANG L R, XU Q H. 辨证治疗中风性痴呆32例 [J]. Academic Periodical of Changchun College of Traditional Chinese Medicine, 1995 (2): 18 (in Chinese).

    [4] GAO X Y, WANG W Q, WEI S L, et al. Review of pharmacological effects of Glycyrrhiza Radix and its bioactive compounds [J]. China Journal of Chinese Materia Medica, 2009, 34 (21): 2695 (in Chinese).

    [5] ZHAO Y, PENG L, GAO Y G, et al. Study on AChE, ACE, α-glycosidase inhibitory activity and nitrite scavenging activity of the licorice extracts [J]. Science and Technology of Food Industry, 2016, 37 (10): 185 (in Chinese).

    [6] ZHAO Z F, CHEN X F, XIE J, et al. Network pharmacology of Polygalae Radix and Gastrodiae Rhizoma in treating epilepsy [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2019, 25 (14): 207 (in Chinese).

    [7] ZHAO ZF, WU N, TIAN X, et al. Chemical constituents, biological activities and quality control of plants from genus Pyrola [J]. China Journal of Chinese Materia Medica, 2017, 42 (4): 618 (in Chinese).

    [8] ZHANG Q, YE M. Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice) [J]. J Chromatogr A, 2009, 1216 (11): 1954.

    [9] PASTORINO G, CORNARA L, SOARES S, et al. Liquorice (Glycyrrhiza glabra): a phytochemical and pharmacological review [J]. Phytother Res, 2018, 32 (12): 2323.

    [10] KAO T C, WU C H, YEN G C. Bioactivity and potential health benefits of licorice [J]. J Agric Food Chem, 2014, 62 (3): 542.

    [11] XUE R, FANG Z, ZHANG M, et al. TCMID: traditional Chinese medicine integrative database for herb molecular mechanism analysis [J]. Nucleic Acids Res, 2013, 41 (Database issue): D1089.

    [12] RU J, LI P, WANG J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines [J]. J Cheminform, 2014, 6 (1): 13.

    [13] ZHANG J F, LI Y C, XIA G Y, et al. Construction and application of pharmacophore model of human carboxylesterase 2 inhibitors [J]. China Journal of Chinese Materia Medica, 2019, doi: 10.19540/j.cnki.cjcmm.20190603.203 (in Chinese).

    [14] ZHAO B W, ZHANG X H, GU Y, et al. Anti-platelet aggregation mechanism of Xixian Tongshuan Preparation based on molecular simulation methods [J]. China Journal of Chinese Materia Medica, 2019, 44 (9): 1882 (in Chinese).

    [15] JIA P, SHENG R, ZHANG J, et al. Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors [J]. Eur J Med Chem, 2009, 44 (2): 772.

    [16] KHALID H, URREHMAN A, ABBASI M A, et al. Synthesis, biological evaluation, and molecular docking of N′-(aryl/alkylsulfonyl)-1-(phenylsulfonyl) piperidine-4-carbohydrazide derivatives [J]. Turk J Chem, 2014, 38 (2): 189.

    [17] XING W, FU Y, SHI Z, et al. Discovery of novel 2,6-disubstituted pyridazinone derivatives as acetylcholinesterase inhibitors [J]. Eur J Med Chem, 2013, 63: 95.

    [18] VAN GREUNEN D G, JOHAN V D W C, CORDIER W, et al. Novel N-benzylpiperidine carboxamide derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer’s disease [J]. Eur J Med Chem, 2019, 179: 680.

    [19] ISMAIL M M, KAMEL M M, MOHAMED L W, et al. Synthesis of new indole derivatives structurally related to donepezil and their biological evaluation as acetylcholinesterase inhibitors [J]. Molecules, 2012, 17 (5): 4811.

    [20] CHEUNG J, RUDOLPH M J, BURSHTEYN F, et al. Structures of human acetylcholinesterase in complex with pharmacologically important ligands [J]. J Med Chem, 2012, 55 (22): 10282.

    [21] KAO T C, WU C H, YEN G C. Bioactivity and potential health benefits of licorice [J]. J Agric Food Chem, 2014, 62(3):542.

    [22] PASTORINO G, CORNARA L, SOARES S, et al. Liquorice (Glycyrrhiza glabra): a phytochemical and pharmacological review [J]. Phytother Res, 2018, 32 (12): 2323.

    [23] TANG Z H, LI T, TONG Y G, et al. A systematic review of the anticancer properties of compounds isolated from licorice (Gancao) [J]. Planta Med, 2015, 81 (18): 1670.

    [24] JI S, LI Z, SONG W, et al. Bioactive constituents of Glycyrrhiza uralensis (Licorice): discovery of the effective components of a traditional herbal medicine [J]. J Nat Prod, 2016, 79 (2): 281.

    [25] BAO F, BAI H Y, WU Z R, et al. Phenolic compounds from cultivated Glycyrrhiza uralensis and their PD-1/PD-L1 inhibitory activities [J]. Nat Prod Res, 2019, doi: org/10.1080/14786419.2019.1586698.

    [26] CEVIK D, KAN Y, KIRMIZIBEKMEZ H. Mechanisms of action of cytotoxic phenolic compounds from Glycyrrhiza iconica roots [J]. Phytomedicine, 2019, 58: 152872.

    [27] HE M, WU H, NIE J, et al. Accurate recognition and feature qualify for flavonoid extracts from liang-wai Gan Cao by liquid chromatography-high resolution-mass spectrometry and computational MS/MS fragmentation [J]. J Pharm Biomed Anal, 2017, 146:37.

    [28] ZHANG L, LI D, CAO F, et al. Identification of human acetylcholinesterase inhibitors from the constituents of EGb761 by modeling docking and molecular dynamics simulations [J]. Comb Chem High T Scr, 2018, 21 (1): 41.

    [29] VITOROVIC-TODOROVIC M D, WOREK F, PERDIH A, et al. The in vitro protective effects of the three novel nanomolar reversible inhibitors of human cholinesterases against irreversible inhibition by organophosphorous chemical warfare agents [J]. Chem Biol Interact, 2019, 309: 108714.

    [30] SARAVANARAMAN P, CHINNADURAI R K, BOOPATHY R. A new role for the nonpathogenic nonsynonymous single-nucleotide polymorphisms of acetylcholinesterase in the treatment of Alzheimer′s disease: a computational study [J]. J Comput Biol, 2014, 21 (8): 632.

    [31] JEYAKUMAR M, SATHYA S, GANDHI S, et al. alpha-Bisabolol beta-D-fucopyranoside as a potential modulator of beta-amyloid peptide induced neurotoxicity: an in vitro & in silico study [J]. Bioorg Chem, 2019, 88: 102935.

    [32] POSRI P, SUTHIWONG J, TAKOMTHONG P, et al. A new flavonoid from the leaves of Atalantia monophylla (L.) DC [J]. Nat Prod Res, 2019, 33 (8): 1115.

    [33] LIU S, CAO XL, LIU G Q, et al. The in silico and in vivo evaluation of puerarin against Alzheimer’s disease [J]. Food Funct, 2019, 10 (2): 799.

    [34] YU Z H, ZHANG C Y, PU B H, et al. Ginkgo Leaves Tablet improved the memory quotient of patients with mild cognitive impairment: a clinical observation [J]. Chinese Journal of Integrated Traditional and Western Medicine, 2014, 34 (3): 287 (in Chinese).

    [35] ZENG P P, LI H D, LIU T. Meta-analysis of oral preparation of Ginkgo Biloba extract in the treatment of mid cognitive impairment [J]. Herald of Medicine, 2017, 36 (7): 761 (in Chinese).

    [36] LU Y W, CHANG L J. 多奈哌齐与银杏叶片治疗老年痴呆的效果对比 [J]. Chinese Journal of Practical Nervous Diseases, 2017, 20 (11): 111 (in Chinese).

This Article



Vol 45, No. 10, Pages 2431-2438

May 2020


Article Outline


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