Cytotoxic Physalins from Aeroponically Grown Physalis acutifolia.

Abstract

Aeroponically grown Physalis acutifolia afforded five new and six known withanolides including 10 physalins. The structures of the new withanolides, acutifolactone (1), 5β,6β-epoxyphysalin C (2), 5α-chloro-6β-hydroxyphysalin C (3), and an inseparable mixture of 5β,6β-epoxy-2,3-dihydrophysalin F-3β-O-sulfate (4) and 5β,6β-epoxy-2,3-dihydrophysalin C-3β-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 μM. These data provided some preliminary structure-activity relationships and suggested that the mechanism of cytotoxic activity of physalins may differ from other classes of withanolides.