RESUMEN
Penta-N-methyl and hexa-N-methyl analogues of RA-VII, an antitumor bicyclic hexapeptide of plant origin, were prepared. In the former, the nitrogens of d-Ala-1 and Ala-4 and in the latter, those of d-Ala-1, Ala-2, and Ala-4 were methylated under the phase-transfer catalysis conditions. Their solution structures were established by NOESY experiments and the crystal structures by X-ray crystallography. Those two methylated analogues showed much weaker cytotoxicity against P-388 leukemia cells than the parent RA-VII.
Asunto(s)
Oligopéptidos/química , Oligopéptidos/farmacología , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Cristalografía por Rayos X , Humanos , Leucemia P388/tratamiento farmacológico , Ratones , Conformación Molecular , Rubia/químicaRESUMEN
A new bicyclic peptide of RA-series, RA-XVIII (3), was isolated from the roots of Rubia cordifolia L. Its structure was established to be a hydroxylated derivative of RA-VII by the semi-synthesis of 3 from deoxybouvardin, and its cytotoxicity against P-388 cells was 0.012 microg/mL.
Asunto(s)
Compuestos Bicíclicos con Puentes/química , Compuestos Bicíclicos con Puentes/farmacología , Oligopéptidos/química , Oligopéptidos/farmacología , Rubia/química , Compuestos Bicíclicos con Puentes/síntesis química , Línea Celular Tumoral , Humanos , Oligopéptidos/síntesis química , Conformación ProteicaRESUMEN
An analogue of an antitumor bicyclic hexapeptide RA-VII was prepared, in which the Ala-2 and Tyr-3 residues of RA-VII were replaced by a cycloisodityrosine unit. In the crystalline state, the peptide backbone structures and the side-chain conformations at Tyr-3, Tyr-5, and Tyr-6 of this analogue and of RA-II were very similar. This analogue, however, showed much weaker cytotoxicity against P-388 leukemia cells than parent RA-VII.
Asunto(s)
Péptidos Cíclicos/síntesis química , Péptidos Cíclicos/farmacología , Química Farmacéutica/métodos , Cristalografía por Rayos X/métodos , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Espectroscopía de Resonancia Magnética , Modelos Químicos , Conformación Molecular , Péptidos/química , Péptidos Cíclicos/química , Extractos Vegetales/metabolismo , Rubia/metabolismo , Tirosina/químicaRESUMEN
The new tuberculosis (TB) lead ecumicin (1), a cyclic tridecapeptide, was isolated from Nonomuraea sp. MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS(2). Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey's analysis.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Péptidos Cíclicos/síntesis química , Péptidos Cíclicos/farmacología , Tuberculosis/tratamiento farmacológico , Antineoplásicos/química , Cromatografía Liquida , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Conformación Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Péptidos Cíclicos/químicaRESUMEN
The purpose of this study was to examine the antiobesity effects of Monascus pilosus-fermented black soybean (F-BS) in C57BL/6 mice with high-fat diet (HFD)-induced obesity. F-BS (oral, 0.5 and 1.0 g/kg per body weight, twice per day) ameliorated obesity by reducing body and liver weight increases, and regulating blood glucose and cholesterol levels in C57BL/6 mice fed a control or HFD with oral administration of F-BS for 12 weeks. F-BS suppressed the growth of epididymal, retroperitoneal, and perirenal fat pads by preventing increases in the adipocyte size. Moreover, the levels of blood glucose, total cholesterol, and leptin were significantly lowered by F-BS administration in a dose-dependent manner. These results indicated that F-BS is a beneficial food supplement for preventing obesity, controlling blood glucose, and lowering cholesterol. Future research strategies should address the mechanisms that selectively regulate obesity, including hyperglycemia and hypercholesterolemia.
Asunto(s)
Tejido Adiposo/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Fermentación , Glycine max , Monascus/metabolismo , Obesidad/dietoterapia , Extractos Vegetales/uso terapéutico , Adipocitos/efectos de los fármacos , Tejido Adiposo/citología , Animales , Fármacos Antiobesidad , Glucemia/metabolismo , Colesterol/sangre , Relación Dosis-Respuesta a Droga , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Leptina/sangre , Hígado/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Obesidad/etiología , Extractos Vegetales/farmacología , Alimentos de Soja , Aumento de Peso/efectos de los fármacosRESUMEN
Two new bicyclic hexapeptides, RA-XXIII and RA-XXIV, were isolated from the roots of Rubia cordifolia L. (Rubiaceae). Their structures were determined by the analysis of their 2D NMR spectra, chemical methods, and X-ray crystallography. The IC50 values of RA-XXIII and RA-XXIV against P-388 leukemia cells were 0.16 and 0.48 microg/ml, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Péptidos Cíclicos/farmacología , Rubia/química , Amoníaco/química , Bromo/química , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Metilación , Péptidos Cíclicos/aislamiento & purificación , Raíces de Plantas/química , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
Two new phenylpropanoid glycosides, scrophulosides A (1) and B (2), were isolated from the rhizomes of Neopicrorhiza scrophulariiflora (Scrophulariaceae), along with two known compounds, androsin (3) and picroside I. Their structures were elucidated on the basis of both chemical and spectroscopic data.