In silico repurposing of antipsychotic drugs for Alzheimer’s disease
Open accessAbstract
BACKGROUND: Alzheimer's disease (AD) is the most prevalent form of dementia and represents one of the highest unmet requirements in medicine today. There is shortage of novel molecules entering into market because of poor pharmacokinetic properties and safety issues. Drug repurposing offers an opportunity to reinvigorate the slowing drug discovery process by finding new uses for existing drugs. The major advantage of the drug repurposing approach is that the safety issues are already investigated in the clinical trials and the drugs are commercially available in the marketplace. As this approach provides an effective solution to hasten the process of providing new alternative drugs for AD, the current study shows the molecular interaction of already known antipsychotic drugs with the different protein targets implicated in AD using in silico studies. RESULT: A computational method based on ligand-protein interaction was adopted in present study to explore potential antipsychotic drugs for the treatment of AD. The screening of approximately 150 antipsychotic drugs was performed on five major protein targets (AChE, BuChE, BACE 1, MAO and NMDA) by molecular docking. In this study, for each protein target, the best drug was identified on the basis of dock score and glide energy. The top hits were then compared with the already known inhibitor of the respective proteins. Some of the drugs showed relatively better docking score and binding energies as compared to the already known inhibitors of the respective targets. Molecular descriptors like molecular weight, number of hydrogen bond donors, acceptors, predicted octanol/water partition coefficient and percentage human oral absorption were also analysed to determine the in silico ADME properties of these drugs and all were found in the acceptable range and follows Lipinski's rule. CONCLUSION: The present study have led to unravel the potential of leading antipsychotic drugs such as pimozide, bromperidol, melperone, anisoperidone, benperidol and anisopirol against multiple targets associated with AD. Benperidol was found to be the best candidate drug interacting with different target proteins involved in AD.
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The docking protocol was validated by re-docking the cocrystallized ligands to the binding site of the target enzyme, as described in a previous study.
“Validation of docking protocol was done as described in the previous study, by re-docking the cocrystallized ligands to the binding site of the target enzyme (Kumar et al., 2017).”
From Alpha-terpinyl acetate: A natural monoterpenoid from Elettaria cardamomum as multi-target directed ligand in Alzheimer’s disease (2020) · cites this paper as Kumar et al., 2017
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Repurposed agents in the Alzheimer’s disease drug development pipeline
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Self-citation
- Authors
- Kumar, S., Chowdhury, S., & Kumar, S.
- Affiliations
- Guru Gobind Singh Indraprastha University (IN)
- Corresponding author
- Kumar, Suresh
- Venue
- BMC Neuroscience
- Published
- 2017-10-27
- Volume
- 18
- Issue
- 1
- Pages
- 76-76
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC5660441
- OpenAlex
- W2765951174
- Cited by
- 103
- References
- 56
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 12 · 2023: 15 · 2022: 19 · 2021: 14 · 2020: 16 · 2019: 9 · 2018: 4
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Faculty Research Grant Scheme, GGSIPU (GGSIPU/DRC)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, drug repurposing, antipsychotic drugs, protein-ligand interactions, acetylcholinesterase, butyrylcholinesterase, beta-secretase, monoamine oxidase, NMDA receptor, benperidol, pimozide, bromperidol, melperone, ADME properties, Lipinski's rule, molecular docking
- MeSH terms
- Acetylcholinesterase, Alzheimer Disease, Butyrophenones, Butyrylcholinesterase, Glucosides, Haloperidol, Humans, Monoamine Oxidase, Pimozide, Psychotropic Drugs, Antipsychotic Agents, Molecular Structure, Receptors, N-Methyl-D-Aspartate, Aspartic Acid Endopeptidases, Norisoprenoids, Amyloid Precursor Protein Secretases, Drug Repositioning, Molecular Docking Simulation
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