Cytotoxicity of derivatives from dehydrocrotonin on V79 cells and Escherichia coli.
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.
Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6110, Campinas SP 13083-970, Brazil. marcela@reitoria.unicamp.br
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da Silva Melo
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Durán
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Haun
D000818:Animals; D002452:Cell Count; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004224:Diterpenes / Q000633:toxicity*; D045785:Diterpenes, Clerodane; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009499:Neutral Red / Q000378:metabolism; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D009696:Nucleic Acids / Q000032:analysis; D010946:Plants, Medicinal / Q000633:toxicity*; D018675:Toxicity Tests
D004224:Diterpenes; D045785:Diterpenes, Clerodane; D009696:Nucleic Acids; C103060:dehydrocrotonin; D009499:Neutral Red; D009580:Nitroblue Tetrazolium