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.
CITATION STYLE
Esteves-Souza, A., Pissinate, K., Maciel, M. A. M., & Echevarria, A. (2018). Synthesis of new trans-dehydrocrotonin nitrogenated derivatives and their cytotoxic and DNA-Topoisomerase I inhibitory activities. Journal of the Brazilian Chemical Society, 29(1), 133–139. https://doi.org/10.21577/0103-5053.20170121
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