RESUMO
Three new diarylpropanes (1-3), including two diarylpropane glycosides, and three known ones, were isolated from 70% aqueous acetone extract of the twigs and leaves of Horsfieldia kingii. Their structures were elucidated by spectroscopic analysis. Bioactive evaluation of inhibition on DDC enzyme assay showed that the new compounds were inactive.
Assuntos
Flavonoides/isolamento & purificação , Myristicaceae/química , Inibidores das Descarboxilases de Aminoácidos Aromáticos/química , Inibidores das Descarboxilases de Aminoácidos Aromáticos/farmacologia , Dopa Descarboxilase/metabolismo , Flavonoides/química , Flavonoides/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Extratos Vegetais/química , Folhas de Planta/química , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
DOPA decarboxylase (DDC) is responsible for the decarboxylation of l-DOPA and related aromatic amino acids and correlates closely with a number of clinical disorders. Sanguinarine, a natural quaternary benzophenanthridine alkaloid (QBA), was reported to be inhibitor of rat DDC and possessed a different inhibitory mechanism. In this study, several natural QBAs were assayed as human DDC inhibitors for the first time. A series of 5-methyl phenanthridium derivatives that contain the basic core structure of QBAs were also synthesized and evaluated as human DDC inhibitors. The title compounds still possessed DDC inhibitory potential. Among the synthesized compounds, 2-hydroxyl-8-methoxy-5-methylphenanthridinium chloride (11k) showed good inhibitory activity with an IC50 value of 0.12mM. Preliminary structure-activity relationship indicated that DDC inhibitory potential of 5-methyl phenanthridium derivatives correlated with the π-electro densities on CN double bond of iminium cation. The hydroxyl group on compound 11k possibly contributed to the formation of hydrogen bond between DDC and the inhibitor.