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Letters in Drug Design & Discovery


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

Research Article

Docking Study on Caspase 3 Inhibitors As Potential Drugs For Traumatic Brain Cell Apoptosis

Author(s): Sajad Najafi, Abbas Alibakhshi, Karim Mahnam and Javad Ranjbari*

Volume 21, Issue 3, 2024

Published on: 25 October, 2022

Page: [542 - 551] Pages: 10

DOI: 10.2174/1570180819666220915101829

Price: $65


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 in silico 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.

Keywords: Caspase 3, apoptosis, virtual screening, docking, MD simulation, MM/PBSA binding free energy.

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