RESUMO
Cardiovascular diseases represent a major cause of disability and death worldwide. Therapeutics are available, but they often have unsatisfactory results and may produce side effects. Alternative treatments based on the use of natural products have been extensively investigated, because of their low toxicity and side effects. Marine organisms are prime candidates for such products, as they are sources of numerous and complex substances with ecological and pharmacological effects. In this work, we investigated, through in vitro experiments, the effects of three diterpenes (pachydictyol A, isopachydictyol A and dichotomanol) from the Brazilian marine alga, Dictyota menstrualis, on platelet aggregation and plasma coagulation. Results showed that dichotomanol inhibited ADP- or collagen-induced aggregation of platelet-rich plasma (PRP), but failed to inhibit washed platelets (WP). In contrast, pachydictyol A and isopachydictyol A failed to inhibit the aggregation of PRP, but inhibited WP aggregation induced by collagen or thrombin. These diterpenes also inhibited coagulation analyzed by the prothrombin time and activated partial thromboplastin time and on commercial fibrinogen. Moreover, diterpenes inhibited the catalytic activity of thrombin. Theoretical studies using the Osiris Property Explorer software showed that diterpenes have low theoretical toxicity profiles and a drug-score similar to commercial anticoagulant drugs. In conclusion, these diterpenes are promising candidates for use in anticoagulant therapy, and this study also highlights the biotechnological potential of oceans and the importance of bioprospecting to develop medicines.
Assuntos
Anticoagulantes/farmacologia , Diterpenos/farmacologia , Phaeophyceae/química , Inibidores da Agregação Plaquetária/farmacologia , Anticoagulantes/isolamento & purificação , Coagulação Sanguínea/efeitos dos fármacos , Colágeno/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Hidrólise , Técnicas In Vitro , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/isolamento & purificação , Trombina/farmacologiaRESUMO
Marine brown algae of the family Dictyotaceae are rich sources of monocyclic, bicyclic, and tricyclic diterpenes. These molecules are responsible for a wide range of pharmacological and ecological functions, as antitumor and antiviral. Here, we analyzed the effect of the dolastane diterpene (4R, 9S, 14S)-4α-Acetoxy-9ß,14α-dihydroxydolast-1(15),7-diene, isolated from the marine brown alga, Canistrocarpus cervicornis on blood clotting and platelet aggregation. The dolastane diterpene was able to inhibit either plasma or fibrinogen coagulation induced by thrombin as well as delayed coagulation in the recalcification test. The dolastane diterpene impaired, in a concentration-dependent manner platelet aggregation induced by collagen or adenosine diphosphate with no lysis on such cells. Thus, the dolastane diterpene maybe a promising source of natural inhibitors for hemostatic disturbs (clotting and platelet aggregation) leading to the discovery of drugs of potential use as antithrombotic and antiplatelet. In addition, the dolastane diterpene may be used as a molecular model for development of new antithrombotic agents giving new approaches to the management to the treatment of thrombotic disturbs.