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The use of amino acids as acyl substitutents at the 2-amino group of our benzophenone core structure yielded compounds with mainly good to moderate farnesyltransferase inhibitory and moderate antimalarial activity. However, these farnesyltransferase inhibitors display some degree of selectivity towards malarial parasites since there was no cytotoxic activity observed at 70-80 microM.

Three new pimaren diterpenoids, ent-8(14)-pimarene-15R, 16-diol (1), ent-8(14)-pimarene-1alpha,15R,16-triol (2), and (5R, 9S, 10R, 13S, 15S)-ent-8(14)-pimarene-1-oxo-15R,16-diol (3), along with three known diterpenoids (4-6) have been isolated from the stem of mangrove plant Bruguiera gymnorrhiza. The structures of compounds 1-3 were determined by extensive spectroscopic (2D NMR, MS, IR, and CD) analysis, and 3 and 5 showed moderate cytotoxic activities against L-929 and K562, respectively.

Differentiation between specific and nonspecific cytotoxic drugs by means of cell analyzer and immunoassay is described. The determination of antiproliferative, cytotoxic, and apoptotic effects as well as enlargement of cells in response to toxic compounds can be used for the disclosure of compounds with a specific mode of action. The usefulness of the procedure was demonstrated with camptothecin (1) as a cytotoxic drug and established inducer of apoptosis. Aphidicolin (2) and the new compound oxoaphidicolin (3) were shown to display no comparable effect. Isolation and structural data of 3 are reported.

Structural variations of the L-aspartic acid substructure of (S)-N-3-phenoxycinnamoylaspartic acid dimethyl ester which shows a selective antiproliferative activity against THP-1 tumor cells, demonstrated that the L-aspartic acid moiety is absolutely mandatory for antiproliferative activity as well as for selectivity.