Target Based Design of few Tau Protein Inhibitors as Antialzheimers

Alzheimer's Disease (AD) is a progressive, neurodegenerative disorder affecting elderly patients. Cognitive impairment is the primary symptoms associated with this disorder. Recent researches are highly focused on few markers which are thought to be characteristics of AD (abnormal aggregate forming protein e.g. Tau and abnormal plaque forming protein e.g. Amyloid-Beta). The present study aims at targeting one of the key protein, i.e.; glycogen synthase kinase 3 beta; (GSK3 beta) serine/threonine protein kinase that participates in Alzheimer's disease. Considering the molecular architechture of GSK3 beta and the 2D pose view of the primary ligand ANP, (phosphoaminophosphonic acid-adenylate ester) lies within the target, few of its analogs were prepared (ss1-ss6). The docking output clearly demonstrated that the test compound ‘ss1’ with its 20th conformer lying closest to the complementary residue (GLN185), i.e.; 5.71 Å, whereas the distance observed between the co-crystal and GLN 185 was 9.25 Å. Most of the compounds with a minimum of 5–10 poses are in the proximal vicinity of the receptive area. The preliminary study on this novel target was encouraging, hence it needs to be extended further to make it more meaningful.