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Dehydroleucodine, a Sesquiterpene Lactone from Gynoxys verrucosa, Demonstrates Cytotoxic Activity against Human Leukemia Cells

Ordóñez, Paola E., Sharma, Krishan K., Bystrom, Laura M., Alas, Maria A., Enriquez, Raul G., Malagón, Omar, Jones, Darin E., Guzman, Monica L., Compadre, Cesar M.
Journal of natural products 2016 v.79 no.4 pp. 691-696
cytotoxicity, humans, lethal dose 50, mechanism of action, mononuclear leukocytes, myeloid leukemia, neoplasm cells, patients, sesquiterpenoid lactones, traditional medicine, Ecuador
The sesquiterpene lactones dehydroleucodine (1) and leucodine (2) were isolated from Gynoxys verrucosa, a species used in traditional medicine in southern Ecuador. The activity of these compounds was determined against eight acute myeloid leukemia (AML) cell lines and compared with their activity against normal peripheral blood mononuclear cells. Compound 1 showed cytotoxic activity against the tested cell lines, with LD₅₀ values between 5.0 and 18.9 μM. Compound 2 was inactive against all of the tested cell lines, demonstrating that the exocyclic methylene in the lactone ring is required for cytotoxic activity. Importantly, compound 1 induced less toxicity to normal blood cells than to AML cell lines and was active against human AML cell samples from five patients, with an average LD₅₀ of 9.4 μM. Mechanistic assays suggest that compound 1 has a similar mechanism of action to parthenolide (3). Although these compounds have significant structural differences, their lipophilic surface signatures show striking similarities.