Bioactive pregnanes from Nerium oleander.

Three new pregnanes, 21-hydroxypregna-4,6-diene-3,12,20-trione (1), 20R-hydroxypregna-4,6-diene-3,12-dione (2), and 16beta,17beta-epoxy-12beta-hydroxypregna-4,6-diene-3,20-dione (3), were isolated from Nerium oleander, together with two known compounds, 12beta-hydroxypregna-4,6,16-triene-3,20-dione (neridienone A, 4) and 20S,21-dihydroxypregna-4,6-diene-3,12-dione (neridienone B, 5). The structures of compounds 1-3 were established on the basis of their spectroscopic data. The anti-inflammatory activity in vitro of compounds 2-4 was examined on the basis of inhibitory activity against the induction of intercellular adhesion molecule-1 (ICAM-1), and compound 4 was active. The cytotoxic activity of compounds 1-5 was evaluated against four human cell lines, normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), human liver tumor cells (HepG2), and human lung carcinoma cells (A-549). Compound 4 showed significant cell growth inhibition of VA-13 and HepG2 cells. The MDR-reversal activity of compounds 1-5 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 1, 2, and 5 showed significant effects on calcein accumulation.