RESUMEN
Ten new sesquiterpene alcohols of which seven germacranes, a eudesmane, a guaiane and an oplopane were isolated from the aerial parts of Artemisia alba Turra. Their structures and relative stereochemistry were elucidated by spectral methods ((1)H and (13)C NMR, COSY, HSQC, HMBC, NOESY, and MS). In addition, the known 7-hydroxycadin-4-en-3-one, centaureidin and axillarin were found for the first time in the studied species.
Asunto(s)
Artemisia/química , Oxígeno/química , Sesquiterpenos de Eudesmano/aislamiento & purificación , Sesquiterpenos de Guayano/aislamiento & purificación , Sesquiterpenos/aislamiento & purificación , Alcoholes/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Sesquiterpenos/química , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Guayano/químicaRESUMEN
Using an in vitro cell-based assay in a flow-design, we have applied activity-guided screening to search for new bioactive compounds isolated from microorganisms. A first assay employs the stable expression of nuclear factor kappa B (NF-κB) while a second assay utilizes the glucocorticoid receptor (GR) coupled to green fluorescent protein. A specialized assay was implemented for both the translocation of NF-κB and to inhibit the translocation of cytokine-mediated NF-κB. In addition, we developed in a wide palette of cell lines used for a highly specialized GR-translocation assay to detect anti-inflammatory effects. This approach demonstrates the straight-forward combination of cell-based assays arranged with an automated fluorescence microscope. This allows for the direct sorting of extracts which are acting in a pharmaceutically interesting way. Initial results using this technique have led to the detection of new anti-inflammatory steroids from bacterial crude extracts.
Asunto(s)
Antiinflamatorios/farmacología , Bioensayo/métodos , Productos Biológicos/farmacología , Evaluación Preclínica de Medicamentos/métodos , Hidroxiesteroides/farmacología , Receptores de Glucocorticoides/metabolismo , Animales , Antiinflamatorios/metabolismo , Productos Biológicos/metabolismo , Células CHO , Línea Celular , Cricetinae , Cricetulus , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Hidroxiesteroides/metabolismo , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Glucocorticoides/genética , TransfecciónRESUMEN
Nine triterpenoids (neoabiestrines A-I, 1-9) including six rearranged lanostanes (1-6) and a rare cycloart-7-ene (7) were isolated from Abies recurvata together with ten known compounds. Their structures were determined by detailed analysis of NMR and MS spectroscopic data. The absolute configurations of 1 and 8 were determined by Cu-Ka X-ray crystallography. Compound 6 showed potent anti-proliferative effect against THP-1 tumor cells with an IC(50) value of 17.8 µg/mL.