title: Dehydroleucodine, a Sesquiterpene Lactone from Gynoxys verrucosa, Demonstrates Cytotoxic Activity against Human Leukemia Cells.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.|Departamento de Química, Universidad Técnica Particular de Loja , Loja, Ecuador.|Department of Chemistry, University of Arkansas at Little Rock , Little Rock, Arkansas 72205, United States.
authors.forename: Paola E
authors.initials: PE
authors.lastname: Ordóñez
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College , New York, New York 10065, United States.
authors.forename: Krishan K
authors.initials: KK
authors.lastname: Sharma
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College , New York, New York 10065, United States.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Bystrom
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College , New York, New York 10065, United States.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Alas
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México , México DF, México.
authors.forename: Raul G
authors.initials: RG
authors.lastname: Enriquez
authors.affiliation: Departamento de Química, Universidad Técnica Particular de Loja , Loja, Ecuador.
authors.forename: Omar
authors.initials: O
authors.lastname: Malagón
authors.affiliation: Department of Chemistry, University of Arkansas at Little Rock , Little Rock, Arkansas 72205, United States.
authors.forename: Darin E
authors.initials: DE
authors.lastname: Jones
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College , New York, New York 10065, United States.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Guzman
authors.affiliation: Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205, United States.
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Compadre
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D015153:Blotting, Western; D004354:Drug Screening Assays, Antitumor; D004484:Ecuador; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008519:Medicine, Traditional; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D012717:Sesquiterpenes; C000610249:leucodine; C002669:parthenolide; C079949:dehydroleucodine