Avaliação in silico do potencial antitrombótico de dímeros de flavonoides sulfatados

Abstract

Blood clots are an aggregate of cross-linked platelets, stabilized by protein fibers, formed through a regulatory cascade, called coagulation cascade. Heparin is an intracellular sulphated polysaccharide that, when it binds to Antithrombin, a protein that inhibits the coagulation cascade, increases its affinity for thrombin and factor Xa. Heparin is naturally occurring, however, in a insufficient quantity to influence coagulation. Studies indicate that the antithrombotic activity of heparin is associated with the sulphate group, which leads to the inference that sulphated flavonoids may bind to the same receptors as heparin, and therefore, are potential drug candidates against thrombosis. Therefore, this study aimed to evaluate the efficiency of sulfated flavonoid-based molecules against thrombosis-associated proteins through molecular docking simulations, comparing their performance with molecules with known antithrombotic activity, obtained from the BindingDB database. Molecular docking proved to be an effective and reliable method. The proposed molecules showed great affinity of interaction with proteins associated with the coagulation cascade, presenting superior performance to the set of ligands taken by reference. The data corroborate the hypothesis that the molecules proposed here have marked antithrombotic potential and are, therefore, potential candidates for drugs against thrombosis.