Poster Presenter

Predicting the Cholinesterases Binding Sites for Plant Derived Inhibitors: Template to Design a Drug for Symptomatic Treatment of Alzheimer's Disease
Venkatachalam Lakshmi, Reji Granab Roselet and Rathanam Boopathy
India

Central cholinergic system is considered as most important neurotransmitter system involved in regulation of cognitive functions. Cholinergic neuronal loss in hippocampal region is main feature of Alzheimer's disease (AD) and enhancement of central cholinergic activity is presently the mainstay of pharmacotherapy of senile Alzheimer type of Dementia. Cholinesterase inhibitors (ChEIs) are the only drugs so far approved for AD treatment. Therapeutically used inhibitors include natural phytoconstituents and synthetic compounds, synthesized based on template natural phytoconstituents. Also ChEIs have potential roles in Vascular Dementia, Parkinson's Disease and Down Syndrome treatment.

The goal of study was to explore possible binding modes of plant based inhibitors which have been shown to inhibit human acetylcholinesterase (AChE), butyrylcholinesterase (BChE). Major observations from this computational docking study are: The ligands tested bind in similar fashion as that of AChEIs reported at aromatic gorge of enzyme. Although they are completely buried in gorge, some of them are not able to enter as deep as reported earlier. This is probably due to bulky aromatic/steroid part of ligands. The stabilizing interactions between protein and ligand are mainly of hydrophobic nature. The structure of best docked inhibitors can be used as template for designing new, selective and powerful AD drugs.