Identification and Screening of Novel ACE Inhibitors using Computational Approach

Abstract

Use of acetylcholinesterase (AChE) inhibitor in treating the neurological disorders has long been studied due to its potential to cross the endothelial tight junctions, longer bioavailability, and better ability to penetrate skin. Alzheimer's disease is found to have closely related with the decline in the level of neurotransmitters which leads to deterioration of the cholinergic neurons of the neocortex and the hippocampus of the rat's brain. Impairment in the transmission of cholinergic nerve signals results in the formation of senile plaque and neurofibrillary tangles (NFT). As a result, one of the main goals for the development of therapeutic approaches for Alzheimer's disease has been to improve the cholinergic activities of the brain. The discovery of one of the most efficient acetylcholinesterase inhibitors called Donepezil was proved to be a much better approach as compared to other drugs such as physostigmine and Tacrine. In the present study we have focused on the role of 5,6-dimethoxy-2-(piperidin-4-ylmethyl)-2,3-dihydroinden-l-one as an important acetylcholinesterase in the treatment of Alzheimer's disease. We have performed molecular docking to see the interaction of ACE target protein and the inhibitory ligands and further validated the pharmacokinetic properties of the drug via ADME analysis of the drug.