RESUMEN
Excessive breakdown of extracellular matrix by metalloproteinases (MMPs) occurs in many pathological conditions, and thus inhibition of MMP activity might have therapeutic potential. The methanolic extract and the identified compounds from the bark of Tristaniopsis calobuxus Brongniart & Gris (Myrtaceae) were tested on the activity, production, and gene expression of MMP-9. The extract produced a concentration-dependent inhibition (50-95% at 10-50 microg/ml) of MMP-9 activity. The inhibitory activity was retained in the ethyl acetate-soluble fraction (50-95% inhibition at 10-50 microg/ml) which also reduced the release of MMP-9 by mouse peritoneal macrophages up to 80%. In the ethyl acetate-soluble fraction, two active fractions, 5A and 5B were identified. HPLC-MS and NMR analyses of these fractions indicated the presence of gallocatechin, ellagic acid, and its glycoside derivatives. Since the absolute configuration of gallocatechin was not determined, in the next experiments both (+)-gallocatechin (2R,3S) and (-)-gallocatechin (2S,3R) were tested, and (-)-epigallocatechin (2R,3R) was included for comparison. 5A and 5B inhibited MMP-9 secretion, an observation which correlated with the decrease of MMP-9 promoter activity and the downregulation of mRNA levels. All compounds decreased MMP-9 mRNA levels and secretion. Ellagic acid, (+)-gallocatechin and (-)-epigallocatechin, but not (-)gallocatechin inhibited promoter-driven transcription. Thus configuration at C2 (R) of the flavanol seem to be critical for the interaction with the promoter.
Asunto(s)
Flavonoides , Regulación de la Expresión Génica/efectos de los fármacos , Inhibidores de la Metaloproteinasa de la Matriz , Myrtaceae/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Corteza de la Planta/química , Polímeros/aislamiento & purificación , Polímeros/farmacología , Animales , Genes Reporteros , Cinética , Macrófagos Peritoneales/enzimología , Espectroscopía de Resonancia Magnética , Metaloproteinasa 9 de la Matriz/genética , Ratones , Fenoles/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polímeros/química , Polifenoles , Regiones Promotoras Genéticas , ARN Mensajero/genética , Proteínas Recombinantes/antagonistas & inhibidores , Virus 40 de los Simios/genética , TransfecciónRESUMEN
The roots of T. x media Rehd. cv. Hicksii gave three novel analogues of paclitaxel modified at the N-acyl residue (N-debenzoyl-N-alpha-methylbutyryl paclitaxel and N-debenzoyl-N-cinnamoyl paclitaxel, 1b and 1c, respectively) or at the ester group at C-2 (2-debenzoyl-2-tigloyl paclitaxel, 1d). Compounds 1b and 1d showed reduced cytotoxicity and tubulin binding compared to paclitaxel, while 1c retained substantial activity in these assays.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Paclitaxel/análogos & derivados , Árboles/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Cromatografía Liquida , Ensayos de Selección de Medicamentos Antitumorales , Raíces de Plantas/química , Análisis Espectral , Relación Estructura-ActividadRESUMEN
A dichloromethane extract of the roots of Eriosema tuberosum exhibited antifungal activity against Cladosporium cucumerinum and Candida albicans using TLC bioautography. Bioassay-directed fractionation led to the isolation of four new compounds, eriosemaones A-D, together with a known compound, flemichin-D, as the active constituents. Three inactive polyphenols were also isolated after methylation, together with one new chromone, eriosematin. Structures were determined by spectroscopic analysis and from chemical evidence.