Evaluation of Computational Method from Crystallographic Structure of Galantamine for Molecular Modeling of Drug Candidates Anti-Alzheimer’s Disease

摘要

Alzheimer’s disease is a neurodegenerative disorder caused by multiple factors, such as: acetylcholine deficiency at synapses; aggregation of beta-amyloid peptides for the formation of senile plaques in the brain tissue and the formation of neurofibrillary tangles within the neurons.It is an increasingly prevalent disease in the elderly and is gaining increasing importance with social development and increased life expectancy in the world. Currently, there are five drugs approved and available in Brazilian market as anti-Alzheimer drugs, which are tacrine, donepezil,rivastigmine, galantamine and memantine, acting as target-specific drugs to reduce symptoms, but Alzheimer’s disease remains without known cure until today. In an attempt to modify this reality, the scientific community continues to seek more effective drugs, and molecular modeling hasbeen an important tool to accelerate the screening process for potentially active compounds and to obtain specific properties of these potential drugs. Thus, this work analyzed the geometric parameters of the crystallographic structure of galantamine, optimizing it under different computationalmethods aiming at the validation of the best computational method and basis sets when compared to the experimental model. In order to do so, this study used several methods of quantum chemistry, multivariate and statistical analysis, from which it was observed that, among the 15 computationalmethods evaluated, the Hartree-Fock method associated to the 6-31G** basis set was the one that best reproduced the experimental geometric parameters, being therefore the validated method in this work and may help future in silico studies of alkaloids as potential anti-Alzheimer drugs.