INSILCO IDENTIFICATION OF SUITABLE ACETUYLCHOLINESTERASE INHIBITORS FROM MORINDA CITRIFOLIA LINN. WITH REFERENCE TO ALZHEIMER'S DISEASE

摘要

Alzheimer's disease, the most common form of dementia accounting for about 50-60% of the overall cases among persons over 65 years of age is characterized by the progressive decline in cognitive function, mediated through learning and memory. According to Cholinergic hypothesis, AD is caused by reduced synthesis of the neurotransmitter ACh, wherein the AChE levels were increased which causes damage to the cholinergic neurons finally leading to cognitive impairments. Hence, all therapies for AD are targeted at the cholinergic system. In this context, docking studies play key role in computer- aided drug design paradigms. As an attempt to identify such natural cholinomimetic and neuroprotective activities, a set of 25 drug molecules from the phytoconstituents of the plant, Morinda citrifolia Linn. Were collected from PubChem Database. These compounds were docked against human AChE (PDB ID: 1B41 and 1N5R) proteins retrieved from Protein Data Bank were performed by Pyrex Virtual Screening tool (Auto Dock Vina). After docking, among these 25 compounds, the drug molecule Huperizine A (854026) was found to have the highest binding energy with both target proteins viz.1B41 and 1N5R (-10.2- and -10.0 respectively) and it contains best binding affinity and interaction of amino acids on the active site of protein pocket binding region. Hence, Huperizine A was predicted as the best drug molecule with Anticholinesterase activity for AD.