Research

Chemical Sciences

Title :

Lead Optimization of 2-((4-fluorophenyl)(4-(pyrazin-2-yl)piperazin-1-yl)methyl)-6-methoxyphenol as GsK3beta Inhibitors for Alzheimer's Disease Therapeutics Targeting Tauopathy, and Neuroinflammation: In-silico design, synthesis, and Biological Evaluation

Area of research :

Chemical Sciences

Focus area :

Drug Design and Development

Principal Investigator :

Dr. Hari Madhav, Indian Institute of science, Bangalore, Karnataka

Timeline Start Year :

2024

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

Glycogen synthase kinase (GsK3beta) is a multifunctional serine or threonine kinase that regulates glycogen metabolism and functions in cell division, stem cell renewal, apoptosis, differentiation, transcription, and insulin action. It is a key target for developing new anti-Alzheimer agents due to its role in tau oligomerization and neuroinflammation. Alzheimer's disease (AD) is a multifactorial disease, with neurofibrillary tangles due to hyperphosphorylated tau and neuroinflammation being major pathological hallmarks. GsK3beta promotes microglial migration and inflammatory activation, and inhibiting it can increase anti-inflammatory cytokines and decrease pro-inflammatory cytokines. Recently, a structure-guided drug design approach was used to develop molecular hybrids of pyrazine and substituted diphenylmethylpiperazine as multi-target-directed ligands for AD treatment. The proposed study aims to optimize the identified lead molecule 21 for potential GsK3beta inhibitors targeting neuroinflammation and tau oligomerization, potentially targeting multiple disease-causing factors.

Total Budget (INR):

Organizations involved