Density Functional Theory, Molecular Interaction Fields, Pharmacophore, Virtual Screening and Physical Chemistry of the Interactions of Novel Acetylcholinesterase Inhibitors in Alzheimer´s Disease

Alzheimer´s disease (AD) is the most important cause of mental disease in elderly people. The progress of the symptoms of the disease are associated with structural modifications of cholinergic synapses in determined regions of the brain, and consequently the reduction of cholinergic neurotransmission potential. The research on acetylcholinesterase (AChE) has increased due to discoveries indicating the involvement of the enzyme in the formation of the β-amiloid peptide during the pathogenesis of AD. It has been noted that this enzyme plays a key role in acceleration of the senile plaques of β-amiloid peptide which is toxic for the neurons. For the development of new potential inhibitors of the enzyme AChE, different techniques of molecular modeling were used as a strategy for the rational design of pharmaceuticals, having as basis the AChE inhibitors described in the literature in addition to those deposited in the PDB, including some which have been already used for the treatment of AD. The objective is to design and test new potential inhibitors of this therapeutical target, with the aim of obtaining and future optimizing new pharmaceutical candidates for Alzheimer. The objectives extend to proposals of new potential leads, selected from data basis of commercial compounds with properties of pharmaceuticals. The virtual screening tend towards structures of inhibitors already reported in the literature as well as pharmacophoric patterns common to them, to be modeled. Keywords: Alzheimer, virtual screening, AChE, DFT, molecular interaction fields.