INHIBITION OF ACETYLCHOLINESTERASE IN ALZHEIMER’S DISEASE- AN IN SILICO APPROACHAbstract
Alzheimer’s disease (AD) is a progressive degenerative disease of the brain marked by gradual and irreversible declines in cognitive functions. Acetylcholinesterase plays a biological role in the termination of nerve impulse transmissions at cholinergic synapses by rapid hydrolysis of acetylcholine. The deficit levels of acetylcholine lead to poor nerve impulse transmission. Thus the cholinesterase inhibitors would reverse the deficit in acetylcholine levels and consequently reverse the memory impairments characteristic of the disease. In the present work, functionalized coumarin compounds and their derivatives were docked into active site of Acetylcholinesterase using the docking programs GOLD and GLIDE. The compounds were screened using High throughput screening, and further subjected to Induced Fit Docking studies. Further, the QSAR studies revealed the best structure activity relationship and 100% of human oral absorption. The inhibitor compounds also satisfied the PASS (Prediction of Activity Spectra for Substances) results of inhibiting the activity of acetylcholinesterase. The type of interaction they exhibit and the residues with which they interact convey that both the compounds are good inhibitors of Acetylcholinesteraseas they exhibit drug like activity.
Department of Biotechnology and Bioinformatics, Bishop Heber College, Tiruchirappalli-625 017, Tamil Nadu, India
28 January, 2012
27 February, 2012
28 April, 2012
01 May, 2012