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2000
Volume 21, Issue 6
  • ISSN: 1570-1646
  • E-ISSN: 1875-6247

Abstract

Background

Glycogen synthase kinase 3-beta (GSK3-β) is a protein that is linked to the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles, both of which are characteristic of Alzheimer's disease. The enzyme's hyperactivity phosphorylates tau proteins, forming neurofibrillary tangles that impair material transport between axons and dendrites and disrupt neuronal function. GSK3-β impacts amyloid precursor protein production, causing Aβ accumulation and neurodegeneration.

Aim/Objective

This study aimed to investigate the inhibitory mechanism of natural compounds from against GSK3-β.

Methods

Computational approach, extra precision glide docking, and the Maestro molecular interface of Schrodinger suites were utilized to determine the binding free energy of the compounds against the prepared GSK3-β. The compounds' ADME parameters and Lipinski's rule of five were also evaluated. Using AutoQSAR, predictive models were constructed for both protein targets.

Results

Three hit compounds (kaempferol, quercetin, and 5,7,4'-trihydroxy-3,8-dimethoxyflavone) were found in this study. These compounds met the recommended range for the specified ADME parameters and passed the rule of five. Additionally, the hit compounds' predicted pIC values were promising.

Conclusion

Our study suggests that the investigated compounds can be used to design GSK3-β inhibitors.

© 2024 Bentham Science Publishers
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2025-10-01

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Computational Evaluation of Bioactive Compounds from Bryophyllum pinnatum as a Novel GSK3B Inhibitor in Alzheimer's Disease
Curr. Proteomics 21, 893 (2024); https://doi.org/10.2174/0115701646361973250130092523
/content/journals/cp/10.2174/0115701646361973250130092523
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  • Article Type:     Research Article
Keyword(s): Alzheimer's disease; amyloid-beta; computational; GSK3-β; natural compounds; neurodegeneration

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