Estudo in silico do potencial anticoagulante de catequinas sulfatadas

Abstract

Progress in computational research has made it possible for in silico methods to offer epoch making benefits for both regulatory needs and the pharmaceutical industry in evaluating the safety profile of medications. Therefore, the main objective of the work is to evaluate the anticoagulant potential of sulfated catechins through molecular docking, and to carry out an ADMET study, in order to evaluate the main chemical and toxicological characteristics of the molecules studied. The structures of the ligands (catechins) were obtained using the ChemSpider platform, the addition of sulfur trioxide (SO3 - ) was carried out using the Chemsketch software, from this the structures were treated and prepared, to then be used in the processes of molecular docking and redocking, in AutodockTools. The SMILES code generated from Chemsketch was inserted into the SwissADME and pkCSM platforms, and then ADMET data for the compounds studied were obtained. For analysis of physicochemical parameters, Lipinski's rule was used, all sulfated catechins are outside the rule, with D. catechin, a compound that was not modified, being the only one to meet all parameters. Regarding pharmacokinetic parameters, it is important to highlight that sulfated molecules have low gastrointestinal absorption, low skin permeability, high polarity and have the ability to act as a pg-p substrate. Only Epicatechin and Epigallocatechin (EGC), sulfated, were able to inhibit CYP3A4. The compounds studied showed low toxicity and do not have the capacity to be carcinogenic, hepatoxic, or cause skin sensitivity. However, sulfated epigallocatechin, epicatechin and D. catechin had the ability to inhibit the hERG II gene, which could cause heart problems. From the analysis of interactions between the studied ligands and the antithrombin III serpin, it was possible to infer that all sulfated ligands carried out some or all of the main interactions carried out by the pentasaccharide with antithrombin III (Asn 45, Arg 46, Arg 47, Lys 114, Lys 125, Arg 129). Among all the compounds studied, Epicatechin gallate and D. sulfated catechin were those that showed the highest affinity with the target (lowest binding energy). All sulfated compounds, with the exception of sulfated epigallocatechin, epicatechin and D. catechin (which inhibit the hERG II gene), can be administered intravenously, transdermally and intramuscularly.