RESUMO
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.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Tuberculose/tratamento farmacológico , Antineoplásicos/química , Cromatografia Líquida , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/químicaRESUMO
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.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Fermentação , Glycine max , Monascus/metabolismo , Obesidade/dietoterapia , Extratos Vegetais/uso terapêutico , Adipócitos/efeitos dos fármacos , Tecido Adiposo/citologia , Animais , Fármacos Antiobesidade , Glicemia/metabolismo , Colesterol/sangue , Relação Dose-Resposta a Droga , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Leptina/sangue , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Extratos Vegetais/farmacologia , Alimentos de Soja , Aumento de Peso/efeitos dos fármacosRESUMO
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.
Assuntos
Oligopeptídeos/química , Oligopeptídeos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cristalografia por Raios X , Humanos , Leucemia P388/tratamento farmacológico , Camundongos , Conformação Molecular , Rubia/químicaRESUMO
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.
Assuntos
Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Química Farmacêutica/métodos , Cristalografia por Raios X/métodos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Espectroscopia de Ressonância Magnética , Modelos Químicos , Conformação Molecular , Peptídeos/química , Peptídeos Cíclicos/química , Extratos Vegetais/metabolismo , Rubia/metabolismo , Tirosina/químicaRESUMO
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.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Peptídeos Cíclicos/farmacologia , Rubia/química , Amônia/química , Bromo/química , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Metilação , Peptídeos Cíclicos/isolamento & purificação , Raízes de Plantas/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
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.
Assuntos
Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/farmacologia , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Rubia/química , Compostos Bicíclicos com Pontes/síntese química , Linhagem Celular Tumoral , Humanos , Oligopeptídeos/síntese química , Conformação ProteicaRESUMO
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.
