Cytotoxic abietane diterpenes from Hyptis martiusii Benth

From roots of Hyptis martiusii Benth. two tanshinone diterpenes were isolated, the new 7beta-hydroxy-11,14-dioxoabieta-8,12-diene (1) in addition to the known 7alpha-acetoxy-12-hydroxy-11,14-dioxoabieta-8,12-diene (7alpha-acetoxyroyleanone) (2). Structures of 1 and 2 were established by spectroscopic means. The cytotoxic activity against five cancer cell lines was evaluated. Compounds 1 and 2 displayed considerable cytotoxic activity against several cancer cell lines with IC50 values in the range of 3.1 to 11.5 microg/ml and 0.9 to 7.6 microg/ml, respectively. The cytotoxic activity seemed to be related to inhibition of DNA synthesis, as revealed by the reduction of 5-bromo-2'-deoxyuridine incorporation and induction of apoptosis, as indicated by the acridine orange/ethidium bromide assay and morphological changes after 24 h of incubation in leukemic cells.