RESUMO
Dehydroleucodine is a bioactive sesquiterpene lactone. Herein, four dehydroleucodine amino derivatives were synthesized using the amines proline, piperidine, morpholine, and tyramine, and spectroscopic methods and single-crystal X-ray diffraction unambiguously established their structures. The cytotoxic activity of these compounds was evaluated against eight acute myeloid leukemia cell lines, and their toxicity to peripheral blood mononuclear cells was also determined. The proline adduct was the most active compound, it showed anti-leukemic activity, upregulated heme oxygenase 1 (HMOX1) and the primary stress-inducible isoform of the heath shock 70 kDa protein 1 (HSPA1A), and downregulated NFkB1 transcription, it was also found to be about 270 times more water soluble than dehydroleucodine.
Assuntos
Proliferação de Células/efeitos dos fármacos , Lactonas/química , Leucemia Mieloide Aguda/tratamento farmacológico , Leucócitos Mononucleares/efeitos dos fármacos , Sesquiterpenos/química , Linhagem Celular Tumoral , Cristalografia por Raios X , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Heme Oxigenase-1/genética , Humanos , Lactonas/síntese química , Lactonas/farmacologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Morfolinas/química , Subunidade p50 de NF-kappa B/genética , Piperidinas/química , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologia , Tiramina/químicaRESUMO
The Mg-mediated conjugate addition of bromoform to a variety of electron-deficient alkenes has been investigated. In the case of nitrodienes and dibenzylideneacetones, tribromomethylated products were isolated, whereas spiro-cyclopropanated products were obtained with cyclic dibenzylideneketones and 3-olefinic oxindoles. The spiro-cyclopropyl ketones derived from cyclic dibenzylideneketones were successfully transformed into fused furans via the Cloke-Wilson rearrangement.
