RESUMO
Two new (1 and 2) and six known hasubanan alkaloids (3-8) and one morphinane alkaloid (9) were isolated from the leaves of the North Queensland rainforest vine Stephania japonica. The structures of 1 and 2 were determined by interpretation of their 1D and 2D NMR spectra. The hasubanan alkaloids showed affinity for the human delta-opioid receptor with IC(50) values ranging from 0.7 to 46 microM. The compounds were also tested for their affinity to micro- and kappa-opioid receptors and shown to be inactive against kappa-opioid receptors, but were of similar potency against the micro-opioid receptor.
Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Plantas Medicinais/química , Receptores Opioides delta/efeitos dos fármacos , Stephania/química , Alcaloides/química , Austrália , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Receptores Opioides delta/metabolismo , Receptores Opioides kappa/metabolismoRESUMO
Two novel indolizidine alkaloids, grandisine A (1) and B (2), and the known alkaloid (-) isoelaeocarpiline (3) were isolated from the leaves of Elaeocarpus grandis and their structures determined by 1D and 2D NMR spectroscopy. The compounds showed affinity for the human delta-opioid receptor. Grandisine A contains a unique tetracyclic skeleton, while grandisine B possesses the unique combination of isoquinuclidinone and indolizidine groups in one molecule.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Elaeocarpaceae/química , Indolizinas/química , Indolizinas/farmacologia , Receptores Opioides delta/efeitos dos fármacos , Alcaloides/isolamento & purificação , Ligação Competitiva/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Indolizinas/isolamento & purificação , Modelos Moleculares , Conformação Molecular , Oligopeptídeos/antagonistas & inibidores , Folhas de Planta/química , Receptores Opioides delta/química , Relação Estrutura-AtividadeRESUMO
Bioassay-guided fractionation of the MeOH extract of the sponge Oceanapia sp. using the Helicobacter pylori enzyme, aspartyl semialdehyde dehydrogenase, ASD, to detect antibacterial activity, led to the isolation of a new pyridoacridine alkaloid, petrosamine B (1). Petrosamine B is a bright blue compound that is sparingly soluble in many organic solvents. The structure of 1 was determined from detailed NMR studies performed in TFA/D2O. Petrosamine B was found to be a weak inhibitor of ASD with an IC50 of 306 microM.
Assuntos
Acridinas/isolamento & purificação , Aldeído Desidrogenase/antagonistas & inibidores , Alcaloides/isolamento & purificação , Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/isolamento & purificação , Helicobacter pylori/enzimologia , Fenantrenos/isolamento & purificação , Poríferos/química , Acridinas/química , Acridinas/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Animais , Austrália , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Fenantrenos/química , Fenantrenos/farmacologiaRESUMO
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.