Cytotoxic activity and antiproliferative effects of a new semi-synthetic derivative of ent-3 beta-hydroxy-13-epi-manoyl oxide on human leukemic cell lines

Ent-3 beta-hydroxy-13-epi-manoyl oxide (1), was converted to its thiomidazo lide derivative (2) which was tested for its cytotoxic activity against a p anel of established human leukemic cell lines. Compound 2, exhibited cytoto xic activity against 13 of the cell lines tested. Additionally: compound 2 was examined for its effect on the uptake of [H-3]-thymidine as a marker of DNA synthesis and on cell proliferation. The morphology of the cells and t he kind of death induced, was investigated. Flow cytometry experiments on a leukemic cell line was also performed. The results show that the semi- syn thetic compound, showed a significant antiproliferative effect and kills ce lls through the process of apoptosis. The appearence of the apoptotic signs was time and close dependent. From the flow cytometry experiments, a synch ronisation through a delay of the cells in G(0/1), phase seems to take plac e.