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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

In Silico Studies to Develop New GSK3β Inhibitors Effective in the Alzheimer's Disease

Author(s): Gozde Yalcin Ozkat* and Ilkay Yildiz

Volume 19, Issue 8, 2022

Published on: 14 March, 2022

Page: [691 - 705] Pages: 15

DOI: 10.2174/1570180819666220210100813

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Abstract

Background: Alzheimer's disease affects a large part of the world’s population by prolonging the human life span and becoming an economic burden in the health system. Therefore, its treatment becomes more and more important every day. With the insufficiency of existing drug molecules, new drug targets are being searched. The most important of these is the Glycogen Synthase Kinase 3β enzyme, which is thought to be of key importance in Tau hyperphosphorylation and Amyloid β accumulation mechanisms.

Objective: In this research, computational studies were conducted to develop a new GSK3β enzyme inhibitor.

Methods: Leading compounds suitable for pharmacophore models obtained by the 3D QSAR method were scanned in databases. In silico ADME/Tox analyses were performed on the obtained molecules.

Results: Although the three molecules (ENA99104, CNR13756, TIM405938) had strong Dock Scores (42.869, 53.344, and 41.119, respectively) in molecular docking calculations, only the CNR13756 molecule was found successful according to molecular dynamics simulations.

Conclusion: All computational studies have revealed that the CNR13756 molecule can exhibit a therapeutic scaffold property, thus obtaining a selective GSK3β inhibitor with minimal side effects

Keywords: Molecular docking, LigandFit, QSAR, molecular dynamics simulations, AMBER14, in silico ADME/Tox analysis, pharmacophore modeling.

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