Cytotoxic epimeric withaphysalins from leaves of Acnistus arborescens

Abstract Phytochemical analysis of the leaves of ACNISTUS ARBORESCENS (Solanaceae) resulted in the isolation of two new epimeric withaphysalins (17S,20R,22R)-5β,6β:18,20-diepoxy-4β,18-dihydroxy-1-oxowitha-24-enolide (2, 18R and 18S), together with the known withaphysalin F (1, 18R and 18S). Their structures were established by spectroscopic methods, including 2D NMR data and comparison with literature data. Compounds 1 and 2 displayed potent cytotoxic activities against several cancer cell lines with IC 50 values in the range of 0.20 to 1.46 μg/mL for 1 and 0.89 to 8.08 μg/mL for 2. The strong cytotoxicity presented by 1 suggests that in this series of compounds, the 2,3-unsaturated ketone moiety is an important pharmacophoric unit. The cytotoxic activity seemed to be related to DNA synthesis inhibition, as revealed by the reduction of 5-bromo-2′-deoxyuridine incorporation after 24 hours of incubation on leukemic cells.