Design, synthesis and antiproliferative activity of some 3-benzylidene-2,3-dihydro-1-benzopyran-4-ones which display selective toxicity for malignant cells

A series of 3-benzylidene-4-chromanones 1a–l were prepared and their cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 lymphoid leukemia cells were compared to the previously generated biodata in these three assays for the isosteric 2-benzylidene-1-tetralones 2a–l. Over 40% of the compounds in series 1 were more potent than their counterparts in series 2, while equipotency was noted in one-third of the comparisons made. In general the IC50 values of 1a–l towards the human T-lymphocytes were in the low micromolar range. Molecular modelling revealed differences in shapes of representative molecules in series 1 and 2 which may contribute to the variation in cytotoxic potencies. Most of the compounds in series 1 displayed greater potencies towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC, and HPLF normal cells and were well tolerated in mice.

The differences in cytotoxicity between series 1 and 2 are likely influenced by variation in physicochemical properties. Series 1 displayed greater cytotoxicity towards certain neoplasms than various normal cells.Figure optionsDownload as PowerPoint slide