Molecular Docking, Physicochemical Properties, Pharmacokinetics and Toxicity of Flavonoids Present in Euterpe Oleracea Martius

Background: Euterpe oleracea Martius, popularly known as açaí, is a fruit rich in α-tocopherols, fibers, lipids, mineral ions and polyphenols. It is believed that the high content of polyphenols, specially flavonoids, provides several health-promoting effects to the açaí fruit, including anti-inflammatory, immunomodulatory, antinociceptive and antioxidant properties. Most of flavonoids are antioxidant molecules from vegetable origin that act as a trap for free radicals, reacting and neutralizing them, thus offering perspectives in preventing oxidative damage.

Objective: In this study we aim to perform an in silico evaluation of flavonoids present in the pulp and in the oil of Euterpe oleracea Martius, and their potential to represent antioxidant agents.

Methods: First, we selected 16 flavonoid molecules present in Euterpe oleracea Martius pulp and oil, and then their physicochemical properties were analysed with respect to the Lipinski's rule of five. Moreover, we evaluated their pharmacokinetic properties using the QikProp module of the Schrödinger software and their toxicity profile using the DEREK software. Docking simulations in the GOLD 4.1 software and calculation of the pharmacophore hypothesis of molecules were also performed.

Results: Flavonoids present in the açaí pulp, catechin, epicatechin, luteolin, chrisoeriol, taxifolin, apigenin, dihydrokaempferol, isovitexin and vitexin presented good oral bioavailability. Regarding pharmacokinetic properties, the compounds catechin, epicatechin, isovitexin, luteolin, chrisoeriol, taxifolin and isorhamnetina rutinoside presented the best results and high human oral absorption. In the prediction of toxicological properties, compounds isorhamnetin rutinoside and rutin presented alert concerning mutagenicity for hydroxynaphthalene or derivate, and in docking simulations all the compounds presented key interactions with the corresponding targets tested.

Conclusion: The flavonoids catechin, chrysoeriol and taxifolin presented overall best results, allowing such computational results to serve as a theoretical basis for future studies of developing drug candidates for biological tests in vitro and in vivo, which can contribute to the treatment of neurodegenerative diseases.

Keywords: Antioxidants.; Açaí; Euterpe oleracea Martius; Flavonoids.