Cucurbitane-Type Triterpenes with Anti-proliferative Effects on U937 Cells from an Egyptian Natural Medicine, Bryonia cretica: Structures of New Triterpene Glycosides, Bryoniaosides A and B

Abstract

The 90% aqueous ethanol extract of an Egyptian natural medicine, the roots of Bryonia cretica L., was found to exhibit a strong inhibitory effect on the proliferation of human leukemia U937 cells. By bioassay-guided fractionation, we isolated two new cucurbitane-type triterpene glycosides, bryoniaosides A and B, were isolated from the roots of Bryonia cretica L. together with 16 known cucurbitane-type triterpenes and glycosides. The chemical structures of bryoniaosides A and B were determined on the basis of chemical and spectroscopic evidence. Effects of principal cucurbitane-type triterpenes (cucurbitacins B, D, E, and J, 23,24-dihydrocucurbitacins B and E, and hexanorcucurbitacin D) on proliferation of the cells were examined. Cucurbitacins B and E showed the greater cytotoxic effects with IC₅₀ values of 9.2 and 16 nM after 72 h, and their IC₅₀ values were equivalent to that of camptothecin. An α,β-conjugated ketone moiety at the 22—24-positions and an acetoxy group at the 25-position are essential for the strong activity.