RESUMO
Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavonones tend to select against 12-hLO, that isoflavons tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2.
Assuntos
Células Epiteliais/enzimologia , Flavonoides/farmacologia , Inibidores de Lipoxigenase , Inibidores de Lipoxigenase/farmacologia , Reticulócitos/enzimologia , Araquidonato 12-Lipoxigenase/sangue , Araquidonato 12-Lipoxigenase/isolamento & purificação , Araquidonato 15-Lipoxigenase/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos , Flavonoides/síntese química , Flavonoides/química , Humanos , Concentração Inibidora 50 , Isoenzimas/antagonistas & inibidores , Isoenzimas/isolamento & purificação , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/química , Masculino , Modelos Moleculares , Estrutura Molecular , Próstata/enzimologia , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
[reaction: see text] A regioselective synthesis of propargylamines by the coupling of propargyl alcohols with tosylamines and carbamates catalyzed by an air- and moisture-tolerant rhenium-oxo complex is described. The ability to couple functionalized components allows for convergent approaches to nitrogen-containing heterocyclic compounds such as the marine antibiotic pentabromopseudilin. These compounds were assayed against human lipoxygenase and found to be both potent and selective.
