Utilização de docking molecular na avaliação do potencial antidiarreico de metabólitos secundários de psidium guineense swartz (myrtaceae)

Abstract

Plant species have been one of the main sources of resources for humanity, being indispensable for the development of civilizations. Its wide applicability is due to the diversity of molecules produced by its metabolism and the ability to interact in different biological systems. Phytochemistry, a sub-area of Natural Products Chemistry, aims to study secondary metabolites from plants. The species Psidium guineense Swartz belongs to the Myrtaceae family and is popularly known as araçá, araçazeiro, common araçá or araçá-mirim. Its leaves have been traditionally used in Brazil as antidiarrheal, diuretic and against indigestion. Molecular docking is a in silico tool used to assess interactions between a drug candidate and its biological target. Considering the popular use of Psidium guineense Sw. (araçá) to treat diarrhoea cases, the present study aimed to evaluate by molecular docking the interactions between metabolites from P. guineense and the human intestinal protein 4U14, which when activated induces increased intestinal motility and diarrhoea. The target protein structure was obtained from the Protein Data Bank. The binding molecules araçain and quercetin were designed in 3D and submitted to “rigid protein-flexible ligand” coupling using the Autodock VINA system of the PyRx Software. After the docking, the ligands in the most stable conformation were selected and the interactions analysed using the Discovery Software. The results obtained for Quercetin and the target protein showed a binding energy of -8.0 kcal/mol, indicating a high tendency of interaction between the molecule and the protein. The result obtained for Araçaine showed a binding energy of -6.7 kcal/mol indicating a favorable energy release for its interaction with the protein active site, but lower than that observed for quercetin. The results obtained indicate favourable binding of the molecules Araçaine and Quercetin to the evaluated protein. The 4U14 protein is the target of antidiarrheal drugs such as Lorapamide (−7.32 kcal/mol) and Triotopium (-9.2 kcal/mol). The preliminary data obtained in this study suggest that the evaluated metabolites may develop an antidiarrheal effect with a mechanism similar to that observed for the drugs Lorapamide and Triotopium, which may confirm the popular use of araçá fruits and infusions for the treatment of diarrhea.