da Silva Melo P, Durán N, Haun M
Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6110, Campinas SP 13083-970, Brazil.
Toxicology. 2001 Feb 28;159(3):135-41. doi: 10.1016/s0300-483x(00)00417-0.
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 NaBH(4) (compound II), by reducing the cyclohexenone and lactone moieties with LiAlH(4) (compound III) and by transforming the lactone moiety into an amide (compound IV) using dimethylamine. The cytotoxicity of these derivatives from DHC was 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). IC(50) values of 540 and 350 microM were obtained for compound II in the NRU and NAC tests, respectively. Compound III was less toxic than the other DHC derivatives (IC(50)=1800 microM) on V79 cells based on NAC assay. Compound IV showed an IC(50) ranging from 350 to 600 microM 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.
通过用硼氢化钠（NaBH₄）还原脱氢巴豆宁（DHC，化合物I）的环己烯酮部分（化合物II）、用氢化铝锂（LiAlH₄）还原环己烯酮和内酯部分（化合物III）以及使用二甲胺将内酯部分转化为酰胺（化合物IV），合成了具有相同抗溃疡特性但毒性较小的脱氢巴豆宁新衍生物。在V79成纤维细胞系上测定了这些DHC衍生物的细胞毒性。评估了细胞毒性的三个独立终点；即核酸含量（NAC）、四唑盐还原（MTT）和中性红摄取（NRU）。在NRU和NAC试验中，化合物II的IC₅₀值分别为540和350微摩尔。基于NAC测定，化合物III在V79细胞上比其他DHC衍生物毒性更小（IC₅₀ = 1800微摩尔）。基于所评估的三个终点，化合物IV的IC₅₀范围为350至600微摩尔。这三种化合物在V79细胞上比DHC毒性更小。在急性毒性试验中，DHC、化合物II、III和IV均未改变大肠杆菌的呼吸速率。
