New derivatives from dehydrocrotonin (DHC, compound I), with the same anti-ulcerogenic properties but less toxicity were synthesised by reducing the cyclohexenone moiety of DHC with NaBH4 (compound II), by reducing the cyclohexenone and lactone moieties with LiAlH4 (compound III) and by transforming the lactone moiety into an amide (compound IV) using dimethylamine. The cytotoxicity of these derivatives from DHC uas assayed on V79 fibroblast cell line. Three independent endpoints for cytotoxicity were evaluated. namely, the nucleic acid content (NAC), tetrazolium reduction (MTT) and neutral red uptake (NRU). IC50 values of 540 and 350 muM were obtained for compound II in the NRU and NAC tests, respectively. Compound III was less toxic than the other DHC derivatives (IC50 = 1800 muM) on V79 cells based on NAC assay. Compound IV showed an IC50 ranging from 350 to 600 muM based on the three endpoints evaluated. The three compounds were less toxic on V79 cells than DHC. DHC, compounds II, III and IV did not change the respiration rate of Escherichia coli on the acute toxicity assay. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.1593135141