Estudo da inibição da acetilcolinesterase por docking molecular e mfcc: Aplicação no tratamento de Alzheimer.

Abstract

Life Human life expectancy has increased and age-related diseases are becoming evident, one of which is Alzheimer's disease, which is a progressive, neurodegenerative disease, with no cure so far, usually occurs with people over 65 years, it is a type of dementia, of increasing and irreversible cognitive decline and with multiple cognitive deficits, of which one, necessarily, is memory loss. These symptoms are severe enough to impact a person's daily activities. As for the possible causes of the disease, they are still unknown, however, the most common signs are: advancing age and genetic factors. In this sense, the work had as general objective to investigate in silico the interaction properties of some inhibitors, among them: Tacrine, Donepezil, Rivastigmine, Galantamine, Fisostigmine and Memantine, with Acetylcholinesterase. For this, methodologically, the Molecular Docking and the Fractionation Method Molecule with Conjugated Hoods (MFCC) were performed, considering molecular structures extracted from certified databases (DrugBank and Protein Data Bank). In this way, quantum calculations were performed and, through these, it was possible to carry out a quantitative analysis, through ab initio. In view of this, the results showed that all six drugs showed inhibitory activity against Acetylcholesteresterase (AChE), a free energy of binding of all complexes, which were expressively negative, which can affirm that, in a thermodynamic way, the values of energy expenditure were favorable. Through in silico studies, that is, through computational methods, the interaction of drugs with the AChE enzyme obtained significant results from pharmacological problems related to the neurodegenerative disease under study. As a result, the research is relevant, as it consists of obtaining the best conformations of lower energy through molecular docking and MFCC, which were proven by theoretical, physical-chemical and thermodynamic concepts.