ACTIVITY OF EXTRACTS AND ALKALOIDS OF THAI ALSTONIA SPECIES AGAINST HUMAN LUNG-CANCER CELL-LINES

Methanol extracts of root barks of Alstonia macrophylla, A. glaucescen s, and A. scholaris, collected from Thailand, have been assessed for c ytotoxic activity against two human lung cancer cell lines, MOR-P (ade nocarcinoma) and COR-L23 (large cell carcinoma), using the SRB assay. Significant cytotoxic activity was exhibited by the extract of A. macr ophylla on both cell lines. Activity-directed fractionation led to the isolation of a novel indole alkaloid, O-methylmacralstonine, from the most active fraction of A. macrophylla along with four known alkaloid s, talcarpine, villalstonine, pleiocarpamine, and macralstonine. Struc ture elucidation of the novel alkaloid was based on spectroscopic meth ods, especially 2D-NMR. The bisindole villalstonine was found to posse ss pronounced activity on both cell lines with an IC50 value less than 5 mu M, but was about 10(3) times less potent than vinblastine sulpha te. The monomeric alkaloid, talcarpine, was found to be inactive. Plei ocarpamine, O-methylmacralstonine and macralstonine were all considera bly less active than villalstonine.