Abstract

IN SILICO STUDY OF PHARMACOKINETICS AND TOXICITY OF TRYPERPENOID GLYCOSIDIC ASPARAGALIN A

Matheus Nunes Da Rocha, Francisco Rogênio Da Silva Mendes, Emanuelle Machado Marinho, Carlos Lacerda De Morais Filho, Márcia Machado Marinho and Emmanuel Silva Marinho*

ABSTRACT

The search for new drugs has been encouraging the study of several phytochemicals, among which we can highlight the triterpenes, which present different biological activities in humans. In this context, the present work aims to carry out an in silico study of pharmacokinetic parameters (ADMET- absorption, distribution, metabolism and excretion) and toxicological parameters of the anti-schistosomal Asparagalin A glycoside triterpene. The present work followed the following steps:[1] the two-dimensional structure of Asparagalin A was designed to predict the physicochemical properties of pKa and Mass Spectrum,[2] the classic force field calculations MMFF94( generating the most stable conformation of the molecule). After the geometric optimization of the compound,[3] the atomic properties such as valence, partial charge and dipole moment were obtained and the properties of the connections such as distance, rotation and dihedral angle values[4] to analyze the ADME calculations, the molecule file was uploaded in. mol format to the Swiss ADME website where it was possible to determine the viability of the molecule's biosynthesis and its pharmacokinetics.[5] To identify possible target proteins, Swiss Target Prediction[6] the molecule was loaded on the ProTox-II online server for toxicity analysis.Simulation studies indicate that the molecule Asparagalin A has an affinity in the environment, low intestinal absorption, low viability of the drug to be administered orally, it is not inhibited as the enzymes CYP1A2, CYP2C19, CYP2C9, CYP2D6 and CYP3A4, as well as altering the settings as receptor proteins grouped by Family G protein-coupled receptors, it has a level 4 toxicity class, potential for oral ingestion, as an immunotoxic potential. In conclusion, asparagalin A molecule has no indication for pharmacological use, or that it does not discard as a prototype molecule to be modified, generating more viable analogs (drug design).

Keywords: ADMET, Anti-Schistosomal, Molecular Modeling, Toxicity, Triterpenes.