Relação quantitativa entre estrutura química e atividade biológica de substâncias com afinidade pelo Receptor PPARd / Quantitative Structure-Activity Relationship of Substances with Affinity by PPARd Receptor

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

30/09/2009

RESUMO

Diabetes mellitus (DM) and metabolic syndrome (SM) are two chronic diseases that provide lower lifes quality of patients. Both diseases are characterized as a disorder of the metabolism of certain nutrients. DM changes the use of carbohydrates due to the deficiency of insulin secretion, while SM mainly alters the lipid metabolism. These diseases have several causes, consequences and symptoms in common. Therefore, in patients with high gravity, they can be associated. There is no cure for theses diseases and new treatments have been researched. There is a class of biological receptors called peroxisome proliferator-activated receptors (PPARs), which control the metabolism of carbohydrates and lipids. A subclass of these receptors, PPARd, regulates several metabolic processes and the substances that activate it can be used as a new drug candidate for the treatment of DM and SM. QSAR (Quantitative Structure-Activity Relationship) is a technique widely used in drug design and it allows that chemical properties of bioactive substances and measurements of biological activity can be correlated and a statistics/mathematical model is generated. In this study, several PPARd agonists with experimental biological activity were selected for a QSAR study. Electronic, stereochemical, lipophilic properties and topological descriptors were calculated for the selected compounds using theoretical methods, such as the density functional theory (DFT). Fishers weight and principal components analysis (PCA) methods were employed to select the most relevant variables for this study. Next, partial least squares (PLS) method was used to construct the multivariate statistic model, and the best model obtained had 6 PCs, q2=0.81 and r2=0.90. The prediction residues calculated for the compounds in the test-set had low values and this indicates both good internal and external consistency. Therefore, the model obtained in this study can be used to predict the biological activity of new compounds.

ASSUNTO(S)

modelagem molecular diabetes mellitus síndrome metabólica planejamento de substâncias bioativas quimica diabetes mellitus metabolic syndrome ppard drug design theoretical methods molecular modeling.

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