Exploring the Potential of Anti-Alzheimer's Drugs in Inhibiting Insulin Amyloid Fibrillation Using Molecular Docking Approaches

Gharouni, Marzieh; Sangin, Narjes; Nassiri, Mohammadreza; Behnam Rassouli, Reihane; Tohidi, Reza

doi:10.22034/ibhf.2025.521934.1026

Exploring the Potential of Anti-Alzheimer's Drugs in Inhibiting Insulin Amyloid Fibrillation Using Molecular Docking Approaches

Document Type : Original Article

Authors

Marzieh Gharouni ¹

Narjes Sangin ¹

Mohammadreza Nassiri ¹

Reihane Behnam Rassouli ²

Reza Tohidi ³

¹ Research Institute of Biotechnology, Ferdowsi University of Mashhad

² Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad

³ Department of Animal Science, Faculty of Agriculture, University of Torbat-e Jam

10.22034/ibhf.2025.521934.1026

Abstract

This study explores the inhibitory potential of FDA-approved anti-Alzheimer’s drugs on insulin amyloid fibrillation using blind molecular docking. The crystallographic structure of human insulin (PDB ID: 3I3Z) and seventeen known anti-Alzheimer’s compounds were retrieved and processed for docking simulations via QuickVina-W. Key ligand–protein interactions were further analyzed using LigPlot+. The results showed that several compounds, especially Aleplasinin, Tideglusib, and Risperidone, exhibited high binding affinity toward key fibrillation-prone residues such as Val12(B), Glu13(B), Tyr16(B), and Phe24(B). These drugs displayed low binding energies and inhibition constants (Ki), suggesting a strong potential to prevent insulin fibril formation. Their ability to interfere with critical interaction sites could help preserve insulin's native structure and reduce amyloid aggregation. The findings of this study could pave the way for the development of effective combination therapies for the simultaneous treatment of chronic metabolic and neurodegenerative diseases such as type 2 diabetes and Alzheimer's disease. Further in vitro and in vivo studies are recommended to validate the computational outcomes and assess safety and efficacy in biological systems.

Keywords

Insulin Amyloid Fibrillation

Anti-Alzheimer’s Drugs

Molecular Docking

Amyloid Inhibition

Subjects