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, especially flavonoids, provides several health-promoting effects to the açaí fruit, including anti-inflammatory, immunomodulatory, antinociceptive and antioxidant properties. Most of the flavonoids are antioxidant molecules of plant 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 the oil of Euterpe oleracea Martius, evaluating their potential to serve as antioxidant agents.

Methods: Firstly, we selected 16 flavonoids present in Euterpe oleracea Martius pulp and oil, and then their physicochemical properties were analyzed concerning the Lipinski's Rule of Five. Moreover, we evaluated their pharmacokinetic properties using the QikProp module of the Schrödinger software as well as their toxicity profile, using the DEREK software. Docking simulations, using the GOLD 4.1 software, as well as pharmacophoric hypotheses calculation of molecules were also performed.

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

Conclusion: The flavonoids catechin, chrysoeriol, and taxifolin presented the best results according to the evaluation conducted in this study. These computational results can be used as a theoretical basis for future studies concerning the development of drug candidates, as well as to enlighten biological tests in vitro and in vivo, which can contribute to the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.