Abstract
Neurodegenerative diseases like Alzheimer’s have become a growing concern as it is difficult to cure. Tau protein is found to be playing a major role in Alzheimer’s disease, and the majority of drugs that are currently on the market are not only prohibitively expensive but also come packaged with side effects that the body cannot tolerate. Repurposing existing compounds is a successful and optimistic strategy that offers reduced risk and increased possibility. We aim to retrieve the existing drugs and analyze them using in-silico techniques. We have retrieved the compounds from the Selleckchem natural product library, and the ability of the drug to cross Blood Brain Barrier (BBB) and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties were examined using SwissADME. The structure of Tau protein (2MZ7) was then retrieved from PDB, and molecular docking of the compounds was performed using the PyRx-Virtual Screening Tool. Initially, 92 compounds passed the ADMET screening criteria, out of which the compound Ligustroflavone was found to have the most favourable binding affinity without violating Lipinski’s rule of 5 of the compounds in the library.
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Acknowledgements
The authors are grateful to the Department of Genetic Engineering, SRM Institute of Science and Technology, for their whole-hearted help throughout this study. We would like to thank Mr. Sharath Kumar RM for his technical guidance.
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Vasanth Kanth T L and Archi Raha have contributed equally to the work by providing molecular docking data, manuscript writing and editing, and results reported in tables and figure illustrations. Vijay Murali R.M, Rangasamy Kirubakaran and KN Aruljothi assisted in manuscript writing, providing table(s) and analyzing BBB permeability of compounds. Yuvatha N contributed by illustrating figures and assisting in BBB permeability analysis. Kumaran K contributed towards analyzing results and organizing data and manuscripts. ArulJothi KN supervised research planning, analysis of results, manuscript writing and editing.
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Vasanth Kanth, T.L., Raha, A., Vijay Murali, R. et al. Repurposing of clinically proven bioactive compounds for targeted treatment of Alzheimer’s disease using molecular docking approach. In Silico Pharmacol. 11, 33 (2023). https://doi.org/10.1007/s40203-023-00173-1
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DOI: https://doi.org/10.1007/s40203-023-00173-1