ESTUDO DO EFEITO ANTIPLAQUETÁRIO DE UM ANÁLOGO DA GRANDISINA

Abstract

Hemostasis is a physiological process involving a series of adaptive chemical and mechanical phenomena to block vascular injuries through the release of substances with pro- and anticoagulant activities. When hemostasis is imbalanced, thrombus formation may occur. The obstruction of arteries and veins can lead to complications such as Acute Myocardial Infarction (AMI), Stroke, and Pulmonary Thromboembolism (PTE). Given the challenges in treatment, especially considering various adverse effects, the development of new antithrombotic drugs is necessary. This study aims to investigate the antiplatelet action of an isoxazolic analog (AGDZ 6) in an in vitro experimental model. Predictive analysis of oral bioavailability (in silico) of AGDZ 6 was performed using SwissADME® software, while toxicity was assessed with the Osiris® Property Explorer. The in vitro toxicity of AGDZ 6 was evaluated through a trypan blue exclusion assay on platelets. Platelet aggregation studies were conducted via turbidimetry at different concentrations (3.125–100 µM) of AGDZ 6, using ADP and adrenaline as aggregation agents. The measurement of reactive oxygen species (ROS) content was performed using fluorescence. Statistical analysis was conducted through variance analysis (ANOVA) and the Tukey-Kramer test, with significance set at p < 0.05. In silico analyses showed that AGDZ 6 has high gastrointestinal absorption and a low risk of mutagenicity, tumorigenicity, and irritability. Additionally, AGDZ 6 was found to be minimally toxic, as it slightly reduced platelet viability. Platelet aggregation inhibition was significant, averaging 33.33% with ADP and 53.16% with epinephrine at the tested concentrations. AGDZ 6 reduced platelet activation by inhibiting approximately 25.85% of reactive oxygen species (ROS) production. Therefore, AGDZ 6 demonstrated potential antiplatelet activity, as it effectively reduced platelet activation and aggregation.