Molecular Docking Studies, Bioactivity Score Prediction, Drug Likeness Analysis of GSK-3 β Inhibitors: A Target Protein Involved in Alzheimer’s Disease

Akanksha Joshi, Rajesh Kumar and Archit Sharma

Department of Biotechnology, University Institute of Engineering and Technology, Kurukshetra University Kurukshetra, India.

Corresponding Author E-mail: archit.sharma786@gmail.com

DOI : http://dx.doi.org/10.13005/bbra/2650

ABSTRACT: Glycogen synthase kinase 3 β (GSK-3 Beta) is a potential target for developing an effective therapeutic effect in Alzheimer's disease (AD). Currently, no such drug or molecules has been found till date which can cure AD completely. Few drugs such as acetylcholinesterase inhibitors and memantine are ineffective in the later stages of the disease. Therefore, with the advancements in computational biology approaches, it is possible to combat alzheimer’s disease by targeting one of the kinases i.e. GSK-3 β involved in hyper phosphorylation of tau (a reliable marker of neurodegenerative disorders). In this study, we have carried out alzheimer’s structure-based drug designing with GSK-3 β. By applying appropriate docking methodology, we have identified few plant-derived compounds which show enhanced target selectivity than the conventional alzheimer's drug (such as memantine). Here we enumerate the comparison among the current and future AD therapy on the basis of their binding affinities. As a result, a large library of compounds has been screened as potent drug targets. It was also observed that withanolide–A (extracted from roots of withania somnifera) has the potential to emerge as the eventual drug for the AD. Moreover, few other phytocompounds such as celastrol, kenpaullone, quercetin, alsterpaullone have also shown enhanced activity in the decreasing order of their binding affinities.

KEYWORDS: Alzheimer’s disease (AD); Drug Designing; Glycogen Synthase Kinase 3 β (GSK-3 β); Hyperphosphorylation of tau, Memantine; Withanolide-A (Ashwagandha)

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