Cytotoxic Physalins from Aeroponically Grown Physalis acutifolia

Aeroponically grown Physalis acutifolia afforded five new and six known withanolides including 10 physalins. The structures of the new withanolides, acutifolactone (1), 5 beta,6 beta-epoxyphysalin C (2), 5 alpha-chloro-6 beta-hydroxyphysalin C (3), and an inseparable mixture of 5 beta,6 beta-epoxy-2,3-dihydrophysalin F-3 beta-O-sulfate (4) and 5 beta,6 beta-epoxy-2,3-dihydrophysalin C-3 beta-O-sulfate (5), were elucidated by analysis of their spectroscopic data and chemical interconversions. The known withanolides were identified as physalins B (6), D (7), F (8), H (9), I (10), and U (11) by comparison of their spectroscopic data with those reported. Evaluation of 1-11 and the derivatives, 13 and 13a, obtained from 4 and 5 against a panel of four human cancer cell lines [NCI-H460 (non-small-cell lung), SF-268 (CNS glioma), PC-3 (prostate adenocarcinoma), and MCF-7 (breast adenocarcinoma)] and normal human lung fibroblast (WI-38) cells revealed that physalins 2, 3, 8, and 9 exhibited selective cytotoxic activity to at least one of the cancer cell lines tested compared to the normal cells and that 7, 10, and 11 were inactive up to a concentration of 10.0 mu M. These data provided some preliminary structure-activity relationships and suggested that the mechanism of rytotoxic activity of physalins may differ from other classes of withanolides.