Synthesis of New trans-Dehydrocrotonin Nitrogenated Derivatives and their Cytotoxic and DNA-Topoisomerase I Inhibitory Activities
AUTOR(ES)
Esteves-Souza, Andressa, Pissinate, Kenia, Maciel, Maria A. M., Echevarria, Aurea
FONTE
J. Braz. Chem. Soc.
DATA DE PUBLICAÇÃO
2018-01
RESUMO
A new series of 19-nor-clerodane diterpene derivatives was synthesized from the natural trans-dehydrocrotonin obtained from stem barks of Croton cajucara (Euphorbiaceae), a native medicinal plant of the Brazilian Amazon. The new derivatives were obtained by changes in the ketone moiety of trans-dehydrocrotonin leading to nitrogenated derivatives which are: three substituted hydrazine diterpenes, oxime, and methyloxime. The cytotoxic effect of the diterpene derivatives was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against Ehrlich carcinoma and K562 human leukemia cells. The cytotoxic activity of the hydrazine and oxime semi-synthetic derivatives was better than the one of the natural product trans-dehydrocrotonin. Moreover, all diterpenes were tested for their DNA topoisomerase I inhibitory activity, and the most effective one, in general, was observed to the phenyl-hydrazone derivative. Results indicated that the topoisomerase I inhibitory effect is correlated with the cytotoxic activity.
Documentos Relacionados
- Cytotoxic and DNA-topoisomerase effects of lapachol amine derivatives and interactions with DNA
- Coencapsulation of trans-Dehydrocrotonin and trans-Dehydrocrotonin:hydroxypropyl-β-cyclodextrin into Microparticles
- Flavonoids from Annona dioica leaves and their effects in Ehrlich carcinoma cells, DNA-topoisomerase I and II
- Experimental and NMR theoretical methodology applied to geometric analysis of the bioactive clerodane trans-dehydrocrotonin
- Synthesis and evaluation of arylamidine derivatives for new antimicrobial and cytotoxic activities