RESUMEN
Chemical characterization of ethyl acetate extract of Exophiala sp. has afforded the isolation of three compounds including a new isocoumarin named exophiarin (1). Exophiala sp. was obtained from the soil containing dumped organic waste (litter). Initially, LC-UV-MS analysis of the extract of Exophiala sp. revealed the presence of a new compound having molecular weight 438 (1) and previously reported TPI-2 and TPI-5. The novelty was established using advanced database search comprising of biological source, molecular weight and UV profile. 1D, 2D NMR and HRMS data have been used for structure elucidation. Exophiarin with TPI-2 and TPI-5 have displayed moderate improvement in glucose uptake activity when tested in rat skeletal muscle cell line L6.
Asunto(s)
Exophiala/química , Hipoglucemiantes/farmacología , Isocumarinas/farmacología , Animales , Espectroscopía de Resonancia Magnética con Carbono-13 , Isocumarinas/química , Isocumarinas/aislamiento & purificación , Ratones , Peso Molecular , Filogenia , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
A screening program aimed at discovering novel anticancer agents based on natural products led to the selection of koningic acid (KA), known as a potent inhibitor of glycolysis. A method was set up to produce this fungal sesquiterpene lactone in large quantities by fermentation, thus allowing (i) an extensive analysis of its anticancer potential in vitro and in vivo and (ii) the semi-synthesis of analogues to delineate structure-activity relationships. KA was characterized as a potent, but non-selective cytotoxic agent, active under both normoxic and hypoxic conditions and inactive in the A549 lung cancer xenograft model. According to our SAR, the acidic group could be replaced to keep bioactivity but an intact epoxide is essential.