title: Antiplatelet and anticoagulant effects of diterpenes isolated from the marine alga, Dictyota menstrualis.
abstract: 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.
authors.affiliation: Departamento de Biologia Molecular e Celular, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, Centro, Niterói, 24020-141, RJ, Brazil. lauravivimel@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: de Andrade Moura
authors.affiliation: Departamento de Biologia Molecular e Celular, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, Centro, Niterói, 24020-141, RJ, Brazil. anakarol.marqui@gmail.com.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Marqui de Almeida
authors.affiliation: Departamento de Biologia Molecular e Celular, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, Centro, Niterói, 24020-141, RJ, Brazil. thaisadomingos@yahoo.com.br.
authors.forename: Thaisa Francielle Souza
authors.initials: TF
authors.lastname: Domingos
authors.affiliation: Departamento de Biologia Marinha, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, Centro, Niterói, 24001-970, RJ, Brazil.
authors.forename: Fredy
authors.initials: F
authors.lastname: Ortiz-Ramirez
authors.affiliation: Departamento de Biologia Marinha, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, Centro, Niterói, 24001-970, RJ, Brazil. dn.cavalcanti@gmail.com.
authors.forename: Diana Negrão
authors.initials: DN
authors.lastname: Cavalcanti
authors.affiliation: Departamento de Biologia Marinha, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, Centro, Niterói, 24001-970, RJ, Brazil. valerialaneuville@gmail.com.
authors.forename: Valéria Laneuville
authors.initials: VL
authors.lastname: Teixeira
authors.affiliation: Departamento de Biologia Molecular e Celular, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista, s/n, Centro, Niterói, 24020-141, RJ, Brazil. andfuly@vm.uff.br.
authors.forename: André Lopes
authors.initials: AL
authors.lastname: Fuly
mesh_terms: D000925:Anticoagulants / Q000302:isolation & purification / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D000459:Phaeophyceae / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D004224:Diterpenes; D010975:Platelet Aggregation Inhibitors; D003094:Collagen; D013917:Thrombin