title: Antileukemic activity of aminoparthenolide analogs.
abstract: A series of aminoparthenolide analogs have been synthesized through a diastereoselective conjugate addition of several primary and secondary amines to the alpha-methylene-gamma-butyrolactone function of the very lipophilic sesquiterpene lactone, parthenolide. Seventeen of the above amines derivatives were evaluated in a full panel of 60 cancer cell lines for anticancer activity. Compound 12, derived from tyramine, was found to be cytostatic as well as cytotoxic toward acute lymphoblastic leukemia cells (ALL, CCRF-CEM) at nanomolar concentrations, while the (R)-(1,2,3,4-tetrahydro-1-naphthyl)amino derivative 9 was found to be cytostatic toward human anaplastic large T-cell lymphoma (SR) cells at concentrations below 10 nM.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
authors.forename: Shama
authors.initials: S
authors.lastname: Nasim
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy; D008956:Models, Chemical; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C002669:parthenolide