Targeting Glycogen Synthase Kinase-3 (Gsk3β) With Naturally Occurring Phytochemicals (Quercetin and its Modelled Analogue): A Pharmacophore Modelling and Molecular Docking Approach


  • Amaku James Friday Michael Okpara University of Agriculture, Umudike, Abia State Nigeria
  • Victor Okezie Ikpeazu Abia State University, Abia State
  • Ifeanyi Otuokere Michael Okpara University of Agriculture, Umudike, Abia State Nigeria
  • Kalu K. Igwe Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria.


Quercetin, molecular docking, ADMET, bioactive compound, pharmacophore modelling


Communication in Physical Sciences 2020, 5(4): 497-508

Received 25 June 2020/Accepted 29 July 2020

Molecular simulation is a significant tool in drug design and modelling. This work consists of a computational analysis through pharmacophore modelling and molecular docking techniques in order to predict the potential inhibitory activity of quercetin and its analogue.  The quercetin analogue QUT1, QUT2, QUT3, QUT4, QUT5, QUT6, QUT7, Quercetin, QUT8, QUT9 and QUT10 were noticed to have minimum energy values of -6.3 kcal/mol, -5.7 kcal/mol, -5.5 kcal/mol, -5.4 kcal/mol, -5.3 kcal/mol, -5.2 kcal/mol, -5.2 kcal/mol, -5.2 kcal/mol, -5.1 kcal/mol,, -5.0 kcal/mol, and +3.0 kcal/mol respectively.  Hence, QUT1 (7-(2,3-dihydroxycyclopropyl)-2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4H-1-benzopyran-4-one) was selected as the lead molecule.  The ligand-receptor interaction study of the lead molecule revealed that QUT1 interacted with 15 amino acid residues (CYS 199, ALA 83, LEU 132, ASP 133, TYR 134, VAL 135, PRO 136, THR 138, ARG 141, ILE 62, VAL 61, VAL 110, VAL 70, GLN 72 and LEU 188 ) within the pocket of glycogen synthase kinase-3β.  With favourable ADME prediction of the lead molecule, is possible to conclude that 7-(2,3-dihydroxycyclopropyl)-2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4H-1-benzopyran-4-one is a probable drug candidate for any disease in which synthase kinase-3β plays a key role in its cell replication.


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Author Biographies

Amaku James Friday, Michael Okpara University of Agriculture, Umudike, Abia State Nigeria

Department of Chemistry

Victor Okezie Ikpeazu, Abia State University, Abia State

Department of Biochemistry

Ifeanyi Otuokere , Michael Okpara University of Agriculture, Umudike, Abia State Nigeria

Department of Chemistry

Kalu K. Igwe , Michael Okpara University of Agriculture, Umudike, Abia State, Nigeria.

Departmemt of Veterinary Physiology, Pharmacology and Biochemistry


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