Evaluación de un conjunto de cumarinas candidatas a inhibidoras de enzimas fosfolipasas A2 (EC 3.1.1.4) de venenos totales de serpientes

Abstract

Phospholipases A2 (PLA2) hydrolyze membrane phospholipids, releasing long-chain fatty acids, but mainly arachidonic acid (ARA), a precursor to the formation of prostaglandins (PG) and leukotrienes (LT) (pro-inflammatory eicosanoids). A possible and interesting anti-inflammatory treatment could be associated with the development of effective anti-inflammatory drugs in selectively inhibiting PLA2, which would prevent the release of AA and, consequently, the formation of PG and LT. Objective: To evaluate, "in vitro", the activity of a set of coumarins that are potentially inhibitory to phospholipase A2 secreted in snake venoms (sPLA2) and, based on these evaluations, to analyze the chemical structure of these molecules to understand their anti-PLA2 enzymatic activity. Methodology: A bibliographic search was carried out for compounds that have reported inhibitory activity against sPLA2 enzymes, either at an experimental and / or theoretical level. Ten coumarin derivatives synthesized by the organic synthesis group, led by Prof. Dr. Eugenio Uriarte Villares and his collaborators, from the University of Santiago de Compostela (USC), were evaluated for their anti-phospholipid activity. The anti-phospholipid activity of ophidian poisons was evaluated by the N-octanoyl benzoic acid (NOBA) method. Results: The structures of the coumarin set evaluated in this study were efficient in inhibiting the phospholipidic activities of sPLA2 in the total venoms of various species of snakes