RESUMEN
Citrulline, a key amino acid of the urea cycle, has been shown to play a regulatory role in protein and energy metabolism in mammals. We questioned whether N-carbamoyl-putrescine (NCP), the decarboxylated derivative of citrulline, could play a role in the biological properties of this amino acid. To evidence the presence of NCP in mammalian tissues, we developed a sensitive reverse-phase high-performance liquid chromatography (HPLC) with fluorimetric detection method with precolumn dansyl derivatization and solid-phase extraction for the determination of NCP together with polyamines in biological samples. Dansyl NCP was identified with a 5.85-min retention time. Linearity was obtained in a concentration range of 0.125 to 12.5 µM. Intraday and day-to-day relative coefficients of variation ranged from 8.9% to 12.3% and from 14% to 14.3%, respectively. Recovery rates in serum ranged from 75% to 83%. Thereafter, we used this method to search for the presence of NCP in serum, muscle, liver, jejunum, and ileum in rats after both short-term intraperitoneal injection and long-term oral citrulline supplementation. We failed to detect NCP in these animals. These data suggest that NCP is not a significant citrulline metabolite in rats.
Asunto(s)
Cromatografía Líquida de Alta Presión , Cromatografía de Fase Inversa , Citrulina/metabolismo , Putrescina/análogos & derivados , Animales , Citrulina/química , Compuestos de Dansilo/química , Putrescina/análisis , Putrescina/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , Extracción en Fase SólidaRESUMEN
The dual specificity CDC25 phosphatases dephosphorylate two inhibitory phospho-amino acids of cyclin-dependent kinases, a major family of cell cycle regulators. CDC25 inhibitors constitute new anti-mitotic agents with potential anticancer activity. While screening through a collection of natural products derived from marine organisms for CDC25A inhibitors, we purified and identified coscinosulfate 1, a sesquiterpene sulfate from the New Caledonian sponge Coscinoderma matthewsi, along with 4. The purified compound 1 displayed significant inhibitory activity towards CDC25A (IC(50): 3 microM).
Asunto(s)
Antineoplásicos/aislamiento & purificación , Poríferos/química , Terpenos/aislamiento & purificación , Fosfatasas cdc25/antagonistas & inhibidores , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Proteínas Recombinantes de Fusión/antagonistas & inhibidores , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Terpenos/química , Terpenos/farmacologíaRESUMEN
First biosynthetic studies utilizing tetradeuterated precursors indicate that the indole glucosinolate glucobrassicin is not a precursor of the phytoalexin brassinin, and that indole-3-acetaldoxime is an efficient precursor.
Asunto(s)
Brassica/química , Brassica/metabolismo , Glucosinolatos/metabolismo , Indoles/metabolismo , Oximas/metabolismo , Extractos Vegetales/biosíntesis , Extractos Vegetales/metabolismo , Indoles/química , Estructura Molecular , Oximas/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Sesquiterpenos , Terpenos , FitoalexinasRESUMEN
Cystodytes cf. dellechiajei collected off Djerba furnished new lipids, sphingosines 1, as inhibitors of phospholipase A2, along with inactive homologous ceramides 2. Structures were determined by spectroscopic methods and chemical transformations.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Fosfolipasas A/antagonistas & inhibidores , Esfingosina/farmacología , Urocordados/química , Animales , Crotalus , Inhibidores Enzimáticos/química , Modelos Químicos , Fosfolipasas A2 , Esfingosina/química , TúnezRESUMEN
Bioassay-guided fractionation of an extract of Holarrhena floribunda stem, has led to the isolation of the new trichothecenes, 8-dihydrotrichothecinol A (1), loukacinol A (2), and loukacinol B (3), and the known compounds, trichothecolone (4), trichothecin (5), trichothecinol A (6), rosenonolactone (7), 6beta-hydroxyrosenonolactone (8), and rosololactone (9). The structures were determined by spectral and chemical methods, and absolute configurations were established by a modified Horeau's method using HPLC. Compounds 1 and 6 exhibited significant cytotoxicity against several human tumor cell lines, whereas compound 8 showed moderate and weak antileishmanial activity toward extracellular and intracellular Leishmania donovani, respectively.
Asunto(s)
Plantas Medicinales/química , Tricotecenos/aislamiento & purificación , Animales , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Análisis Espectral , Tricotecenos/química , Células Tumorales CultivadasRESUMEN
Following feeding experiments with the tetradeuterated cruciferous phytoalexins brassinin (5b) and cyclobrassinin (6b), leaves of Brassica carinata were elicited with the blackleg causing fungus Phoma lingam and incubated. Spectroscopic and HPLC analyses indicated that both brassinin (5a) and cyclobrassinin (6a) were incorporated into the cruciferous phytoalexin brassilexin (7a).