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2000
Volume 21, Issue 3
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background: Apoptosis of brain cells (neurons and glia) has a crucial role in humans' pathology of traumatic brain injury (TBI). So, a decrease in the apoptosis rate can potentially reduce the harmful effects and lead to better functional outcomes. Drug repurposing by computational methodologies like protein-ligand docking allows us to make drug discovery more efficient and less expensive. Objective: In the current study, we used the methodology to study the inhibitory effect of thousands of FDA/non-FDA approved, investigational compounds on caspase 3 as one of the most important members of the cell apoptosis pathway. Methods: Molecular docking and pharmacokinetic properties calculations were done. The molecular dynamics (MD) simulations of all complexes and free caspase 3 were carried out. We carried out docking experiments using methods and docked a pool of medications to the active site of the human caspase-3 X-ray structure. The best compounds were selected and subjected to pharmacokinetic analysis, molecular simulation, and free energy calculations. Results: Finally, 6 components (Naldemedine, Celastrol, Nilotinib, Drospirenone, Lumacaftor, and R- 343) were selected as the best in terms of structural and pharmaceutical properties, low toxicity that can be administered orally for the preclinical and clinical future investigations.

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/content/journals/lddd/10.2174/1570180819666220915101829
2024-03-01
2025-01-06
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/content/journals/lddd/10.2174/1570180819666220915101829
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  • Article Type:
    Research Article
Keyword(s): apoptosis; Caspase 3; docking; MD simulation; MM/PBSA binding free energy; virtual screening
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