Applied Sciences
| Open Access |
DOI: Discovery of Potential Multi-Target Therapeutics for Alzheimer's Disease Through in Silico Drug Repurposing and Molecular Docking: Identification of Withaferin A and Sorafenib as Promising Candidates
Aishwarya Shukla , Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow-226028, India Garima Awasthi , Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow-226028, India Mohit Nigam , Department of Biotechnology, School of Pharmaceutical and Biological Sciences, Harcourt Butler Technical University, Kanpur, U.P., 208002, IndiaAbstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuronal degeneration, and memory impairment. Despite extensive research, effective disease-modifying therapies remain limited. Drug repurposing combined with computational approaches has emerged as a promising strategy for identifying potential therapeutic candidates with reduced development time and cost. The present study employed molecular docking to evaluate the interaction of ten bioactive compounds, Apigenin, Berberine, Curcumin, Huperzine A, Kaempferol, L-Theanine, Quercetin, Resveratrol, Withaferin A, and Sorafenib, with three proteins implicated in AD pathogenesis: Nicastrin, TREM2, and Cystatin C. Protein structures were generated using homology modelling through SWISS-MODEL, and docking simulations were conducted using AutoDock Vina. Binding affinities were evaluated using docking scores (kcal/mol). Among the evaluated compounds, Sorafenib and Withaferin A exhibited the strongest interactions across all targets, particularly with Cystatin C, showing binding energies of -7.7 kcal/mol and -7.6 kcal/mol respectively. Other phytochemicals such as Curcumin, Berberine, and Huperzine A demonstrated moderate binding affinities. These findings indicate that Sorafenib and Withaferin A may act as promising multi-target therapeutic candidates for Alzheimer’s disease. Further experimental validation through in vitro and in vivo studies is necessary to confirm their therapeutic potential.
Keywords
Alzheimer’s disease, drug repurposing, molecular docking, phytochemicals, Nicastrin
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