In Silico Studies to Develop New GSK3 beta Inhibitors Effective in the 's Disease

Ozkat G., YILDIZ İ.

LETTERS IN DRUG DESIGN & DISCOVERY, vol.19, no.8, pp.691-705, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 8
  • Publication Date: 2022
  • Doi Number: 10.2174/1570180819666220210100813
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE
  • Page Numbers: pp.691-705
  • Keywords: Molecular docking, LigandFit, QSAR, molecular dynamics simulations, AMBER14, in silico ADME, Tox analysis, pharmacophore modeling, ALZHEIMERS-DISEASE, PROTEIN, DYSFUNCTION, GSK-3-BETA, TAU
  • Recep Tayyip Erdoğan University Affiliated: Yes


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 3 beta enzyme, which is thought to be of key importance in Tau hyperphosphorylation and Amyloid beta accumulation mechanisms. Objective: In this research, computational studies were conducted to develop a new GSK3 beta 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 GSK3 beta inhibitor with minimal side effects.