RESUMEN
When cultivated under aeroponic growth conditions, Physalis crassifolia produced 11 new withanolides (1-11) and seven known withanolides (12-18) including those obtained from the wild-crafted plant. The structures of the new withanolides were elucidated by the application of spectroscopic techniques, and the known withanolides were identified by comparison of their spectroscopic data with those reported. Withanolides 1-11 and 16 were evaluated for their potential anticancer activity using five tumor cell lines. Of these, the 17ß-hydroxy-18-acetoxywithanolides 1, 2, 6, 7, and 16 showed potent antiproliferative activity, with some having selectivity for prostate adenocarcinoma (LNCaP and PC-3M) compared to the breast adenocarcinoma (MCF-7), non-small-cell lung cancer (NCI-H460), and CNS glioma (SF-268) cell lines used. The cytotoxicity data obtained for 12-15, 17, and 19 have provided additional structure-activity relationship information for the 17ß-hydroxy-18-acetoxywithanolides.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Physalis/química , Neoplasias de la Próstata/tratamiento farmacológico , Witanólidos/aislamiento & purificación , Witanólidos/farmacología , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Masculino , Estructura Molecular , Physalis/crecimiento & desarrollo , Relación Estructura-Actividad , Witanólidos/químicaRESUMEN
In an attempt to maximize production and the structural diversity of plant metabolites, the effect of growing the medicinal plant Withania somnifera under soil-less aeroponic conditions on its ability to produce withaferin A and withanolides was investigated. It resulted in the isolation and characterization of two compounds, 3α-(uracil-1-yl)-2,3-dihydrowithaferin A (1) and 3ß-(adenin-9-yl)-2,3-dihydrowithaferin A (2), in addition to 10 known withanolides including 2,3-dihydrowithaferin A-3ß-O-sulfate. 3ß-O-Butyl-2,3-dihydrowithaferin A (3), presumably an artifact formed from withaferin A during the isolation process was also encountered. Reaction of withaferin A with uracil afforded 1 and its epimer, 3ß-(uracil-1-yl)-2,3-dihydrowithaferin A (4). The structures of these compounds were elucidated on the basis of their high resolution mass and NMR spectroscopic data.