title: Cytotoxic 1,3-diarylidene-2-tetralones and related compounds.
abstract: A number of 1,3-arylidene-2-tetralones 1, 2 and 4 were synthesised and demonstrated cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the related 1-arylidene-2-tetralones 3 possessed lower potencies in these screens than the compounds in series 1 and 4. Approximately, half of the compounds were evaluated against a panel of human tumour cell lines. In this screen, most of the enones were more cytotoxic than the established anticancer agent melphalan and some demonstrated selective toxicity towards leukemic and colon cancer cells. The modes of action of representative compounds include interfering with the biosyntheses of nucleic acids and proteins as well as altering redox potentials. The compounds were well tolerated when administered intraperiteonally to mice. Thus these novel enones are promising prototypic molecules due to their potent cytotoxic properties and lack of significant murine toxicity.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan, Canada S7N 5C9. dimmock@skyway.usask.ca
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
authors.forename: Maniyan P
authors.initials: MP
authors.lastname: Padmanilyam
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Zello
authors.forename: J Wilson
authors.initials: JW
authors.lastname: Quail
authors.forename: Eliud O
authors.initials: EO
authors.lastname: Oloo
authors.forename: Jared S
authors.initials: JS
authors.lastname: Prisciak
authors.forename: Heinz Bernhard
authors.initials: HB
authors.lastname: Kraatz
authors.forename: Arten
authors.initials: A
authors.lastname: Cherkasov
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Lee
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Allen
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Santos
authors.forename: Elias K
authors.initials: EK
authors.lastname: Manavathu
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: James P
authors.initials: JP
authors.lastname: Stables
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry* / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D010084:Oxidation-Reduction; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry* / Q000494:pharmacology*; D013267:Stilbenes / Q000737:chemistry; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones; D011084:Polycyclic Aromatic Hydrocarbons; D013267:Stilbenes; D013764:Tetrahydronaphthalenes