RESUMO
Three new polyether squalene derivatives 15-dehydroxythyrsenol A (2), prethyrsenol A (3) and 13-hydroxyprethyrsenol A (4) have been isolated from the red alga Laurencia viridis. Their structures were determined through the interpretation of NMR spectroscopic data and chemical correlations. In addition, four semi-synthetic compounds modulating the solubility of the lead compound dehydrothyrsiferol (1) were prepared without loss of activity. The cytotoxicity of the new compounds exhibited low µM activities. In order to explain their biological properties, docking simulations of the natural and synthetic compounds onto the αvß3 integrin binding region were carried out.
Assuntos
Apoptose/efeitos dos fármacos , Integrinas/metabolismo , Laurencia/química , Extratos Vegetais/farmacologia , Piranos/química , Esqualeno/química , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia em Gel , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Integrinas/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Extratos Vegetais/química , Ligação Proteica , Piranos/metabolismo , Piranos/farmacologia , Esqualeno/metabolismo , Esqualeno/farmacologia , Relação Estrutura-AtividadeRESUMO
Ten zoanthamine-type alkaloids from two marine zoanthids belonging to the Zoanthus genus (Zoanthus nymphaeus and Zoanthus sp.) along with one semisynthetic derivative were evaluated for their antiplatelet activities on human platelet aggregation induced by several stimulating agents. 11-Hydroxyzoanthamine (11) and a synthetic derivative of norzoanthamine (16) showed strong inhibition against thrombin-, collagen- and arachidonic acid-induced aggregation, zoanthenol (15) displayed a selective inhibitory activity induced by collagen, while zoanthaminone (10) behaved as a potent aggregant agent. These evaluations allowed us to deduce several structure-activity relationships and suggest some mechanisms of action for this type of compounds.