RESUMEN
Two new naphthalene derivatives, named patientosides A (1) and B (2), were isolated from the roots of Rumex patientia. The structures of the new compounds were established as 2-acetyl-4-chloro-1,8-dihydroxy-3-methylnaphthalene-8-O-beta-D-glucopyranoside (1) and 2,4-dichloro-1,8-dihydroxy-3-methylnaphthalene-8-O-beta-D-glucopyranoside (2) by means of spectroscopic methods.
Asunto(s)
Glicósidos/química , Naftalenos/química , Plantas Medicinales/química , Polygonaceae/química , Cromatografía en Capa Delgada , Glicósidos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Naftalenos/aislamiento & purificación , Espectrofotometría Ultravioleta , TurquíaRESUMEN
Three novel and two known naphthalene glycosides were isolated from the roots of Rumex patientia L. (Polygonaceae). The structures of the new compounds were established, respectively as 2-acetyl-3-methyl-6-carboxy-1,8-dihydroxynaphthalene-8-O-beta-D-glucopyranoside, 4,4"-binaphthalene-8,8"-O,O-di-beta-D-glucopyranoside and 2-acetyl-3-methyl-1,8-dihydroxynaphthalene-8-O-beta-D-glucopyranosyl (1-->3) beta-D-glucopyranoside on the basis of spectral analysis. The other napthalene glycosides were determined as nepodin-8-O-beta-D-glucopyranoside and torachrysone-8-O-beta-D-glucopyranoside by comparison of their spectral data with those previously reported.
Asunto(s)
Glicósidos/aislamiento & purificación , Naftalenos/química , Plantas Medicinales/química , Polygonaceae/química , Glicósidos/química , Espectroscopía de Resonancia Magnética , Raíces de Plantas/química , TurquíaRESUMEN
The studies presented were designed to test the efficacy of farnesyltransferase inhibitors (FTIs) as potential chemopreventive compounds in the mouse lung tumor model, and in tumor cell lines. The compounds included manumycin, gliotoxin, dihydroepiandrosterone (DHEA), perillyl alcohol (POH), and FTI-276. Each of these compounds had the potential, based on in vitro and limited in vivo evidence, to inhibit mouse lung tumorigenesis. In vitro studies were conducted with both K-ras-transformed NIH-3T3 cells and mouse lung tumor epithelial cell lines. We utilized 2 primary mouse lung tumor models that reliably produce lung tumors with an oncogenic K-ras mutation when induded by 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK). Manumycin, gliotoxin, DHEA, and POH were administered 3 times per week peritoneally (i.p.), starting 1 week prior to carcinogen treatment, and throughout the test period (4.5 months). FTI-276 was delivered daily for 4 months by a time-release pellet method. Both the manumycin and gliotoxin treatment groups demonstrated 100% incidence and an increase in tumor multiplicity over control, of 66% and 58% increase respectively (P < .05). Although DHEA showed no significant chemopreventive effect, POH treatment demonstrated a 22% reduction in tumor incidence (P < .05) and a 58% reduction in tumor multiplicity (P < .05). Finally, FTI-276 reduced both the tumor multiplicity by 41.7% (P < .005), and the total tumor volume/burden per mouse by 79.4% (P < .0001). The apoptotic index in FTI-276-treated tumors showed an increase of 77% over control tumors (P < .05). In vitro, all compounds demonstrated growth inhibition at a dose-response manner; however, manumycin, gliotoxin, and DHEA demonstrated an initial increase in growth rate at lower doses. In summary, we have shown that POH and FTI-276 are chemopreventive in a primary mouse lung tumor model. In contrast, DHEA was not significantly chemopreventive at the dosage utilized, and treatment of an immunocompetent host with manumycin or gliotoxin demonstrated a significant increase in tumorigenicity over carcinogen control.
Asunto(s)
Adenoma/prevención & control , Transferasas Alquil y Aril/antagonistas & inhibidores , Inhibidores Enzimáticos/uso terapéutico , Neoplasias Pulmonares/prevención & control , Metionina/análogos & derivados , Monoterpenos , Células 3T3 , Adenoma/inducido químicamente , Adenoma/química , Adenoma/patología , Animales , Apoptosis , Quimioprevención , ADN de Neoplasias/análisis , Deshidroepiandrosterona/uso terapéutico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Farnesiltransferasa , Técnica del Anticuerpo Fluorescente Indirecta , Gliotoxina/uso terapéutico , Etiquetado Corte-Fin in Situ , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/química , Neoplasias Pulmonares/patología , Metionina/uso terapéutico , Ratones , Ratones Endogámicos A , Ratones Endogámicos C3H , Polienos/uso terapéutico , Reacción en Cadena de la Polimerasa , Alcamidas Poliinsaturadas , Antígeno Nuclear de Célula en Proliferación/análisis , Terpenos/uso terapéuticoRESUMEN
Pyridazomycin, a new antifungal antibiotic produced by Streptomyces violaceoniger sp. griseofuscus (strain Tü 2557), was detected in a selective screening against Mucor hiemalis (Tü 179/180). The amino acid side chain of 1 can be seen as L-ornithine, whose gamma-nitrogen atom is part of a pyridazine ring building a quaternary ammonium system. The structure of 1 was established by spectroscopic analysis of the parent compound and degradation products. The occurrence of a pyridazine ring in microbial secondary metabolites is unique.