RESUMO
Bioassay-guided fractionation of the methanol extract of the Australian sponge Neopetrosia exigua led to the isolation of exiguaquinol (2), a new pentacyclic hydroquinone that inhibited Helicobacter pylori glutamate racemase (MurI) with an IC(50) of 4.4 microM. Its structure and relative configuration were assigned on the basis of spectroscopic data. Exiguaquinol (2), bearing a novel pentacyclic ring skeleton, is the first natural product to show inhibition of H. pylori MurI. Its protein-ligand modeling is also discussed.
Assuntos
Isomerases de Aminoácido/antagonistas & inibidores , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/enzimologia , Hidroquinonas/isolamento & purificação , Hidroquinonas/farmacologia , Poríferos/química , Animais , Antibacterianos/química , Cristalografia por Raios X , Hidroquinonas/química , Ligantes , Estrutura Molecular , Conformação ProteicaRESUMO
Extracts from dried leaf and stems of Elaeodendron australe var. integrifolium (Celastraceae) collected in South East Queensland, Australia, were active in an assay that measured Ca(2+) driven expression of IL-2/luciferase designed to identify inhibitors of the ICRAC channel. Bioassay-guided isolation using C18 and polyamide column chromatography, HPLC (Phenyl and C18) and centrifugal partition chromatography (CPC) led to the isolation of digitoxigenin (1) and three cardenolide glycosides, glucoside 2, quinovoside 3 and the new natural product xyloside 4, as the active components with low nM activity in the reporter assay.
Assuntos
Canais de Cálcio/metabolismo , Cardenolídeos/farmacologia , Celastraceae/química , Glicosídeos/farmacologia , Cardenolídeos/química , Cardenolídeos/isolamento & purificação , Relação Dose-Resposta a Droga , Glicosídeos/química , Glicosídeos/isolamento & purificação , Conformação Molecular , Folhas de Planta/química , Caules de Planta/química , Relação Estrutura-AtividadeRESUMO
As part of our search for natural products active against the JNK3 kinase, two novel, charged benzylisoquinolines, latifolian A (1) and latifolian B (2), were isolated from the stem bark of the Papua New Guinean vine Gnetum latifolium. The planar structures were determined through detailed 2D NMR analysis. The relative configurations were assigned after examination of the ROESY data and through detailed molecular modeling studies.