RESUMO
Five new diterpenes (1-5) and a megastigmane derivative (6) were isolated from the aerial parts of Euphorbia laurifolia, along with several known compounds. Their structures were elucidated by NMR, MS, and ECD and by chemical methods. A chemical proteomics drug affinity responsive target stability (DARTS) approach to investigate the lathyrane diterpene 1, laurifolioside, on its putative cellular target(s) was performed. Clathrin heavy chain 1, a protein mainly involved in selective uptake of proteins, viruses, and other macromolecules at the plasma membrane of cells, was identified as the major interaction partner of compound 1. The modulation of clathrin activity by 1 was studied through microscopy, molecular docking, and molecular dynamics studies, suggesting a new activity of lathyrane diterpenes in the modulation of trafficking pathways.
Assuntos
Cadeias Pesadas de Clatrina/metabolismo , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Euphorbia/química , Cicloexanonas/química , Cicloexanonas/isolamento & purificação , Cicloexanonas/farmacologia , Diterpenos/química , Equador , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Norisoprenoides/química , Norisoprenoides/isolamento & purificação , Norisoprenoides/farmacologia , Ressonância Magnética Nuclear Biomolecular , Componentes Aéreos da Planta/química , Proteínas de Plantas/análise , Proteínas de Plantas/químicaRESUMO
Three new coumarins (1-3), a prenylated flavanone (4), and two iridoids (5 and 6), together with 17 known secondary metabolites, were isolated from the aerial parts of Arcytophyllum thymifolium. The structures of the new compounds were elucidated on the basis of their spectroscopic data. The potential hypoglycemic properties of the new and known compounds were evaluated by measuring their α-amylase and α-glucosidase inhibitory effects. The iridoid asperulosidic acid (15) and the flavonoid rhamnetin (13) showed the highest activities versus α-amylase (IC50 = 69.4 ± 3.1 and 73.9 ± 5.9 µM, respectively). In turn, the new eriodictyol derivative 4 exhibited the most potent effect as an α-glucosidase inhibitor, with an IC50 value of 28.1 ± 2.6 µM, and was more active than acarbose, used as a positive control. Modeling studies were also performed to suggest the interaction mode of compound 4 in the α-glucosidase enzyme active site.
Assuntos
Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Iridoides/isolamento & purificação , Iridoides/farmacologia , Rubiaceae/química , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Acarbose/farmacologia , Algoritmos , Cumarínicos/química , Equador , Inibidores Enzimáticos/química , Flavanonas , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/química , Iridoides/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Quercetina/análogos & derivados , Quercetina/farmacologiaRESUMO
A bioassay-oriented approach led to the isolation of 11 compounds, including three new natural flavonoids, (2S)-isookanin 7-O-α-L-arabinopyranoside (1), (2S)-isookanin 7-O-(2''-acetyl)-α-L-arabinopyranoside (2), and luteolin 7-O-ß-D-glucopyranosyl-(1 â 6)-ß-D-galactopyranoside (6), from Bidens humilis aerial parts. Their structures were determined via spectroscopic analyses including two-dimensional nuclear magnetic resonance. The antioxidant activity of all compounds was also tested by three different assays. The Relative Antioxidant Capacity Index (RACI) is applied herein, from the perspective of statistics, by integrating the antioxidant capacity data determined by these chemical methods.
Assuntos
Antioxidantes/metabolismo , Bidens/química , Flavonoides/metabolismo , Sequestradores de Radicais Livres/metabolismo , Radicais Livres/metabolismo , Fenóis/metabolismo , Antioxidantes/química , Flavonoides/química , Sequestradores de Radicais Livres/química , Radicais Livres/química , Estrutura Molecular , Oxirredução , Fenóis/química , Componentes Aéreos da Planta/química , Extratos Vegetais/químicaRESUMO
Phytochemical investigation of the extracts of the leaves of Siparuna thecaphora (Poepp. et Endl.) A. DC. (Siparunaceae) allowed the isolation of one monoterpene glycoside, named trans-thujane-1α,7-diol 1-O-ß-D-glucopyranoside (1) along with rutin, quercetin 3-O-ß-D-glucopyranoside and 3,4-dihydroxybenzaldehyde. Their structural characterisation was obtained on the basis of extensive spectroscopic analyses, including 1D and 2D NMR experiments and HR-ESI-MS.