title: Cytotoxic 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes and related compounds.
abstract: A series of 1,4-bis(2-oxo-1-cycloalkylmethylene)benzenes 2a-c and 4 and a related acyclic analogue 6a were synthesised and converted to the corresponding Mannich bases 3a-c, 5 and 6b. Evaluation of these compounds against murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed that the Mannich bases were more cytotoxic than the corresponding unsaturated ketones. 1,4-bis(3-Dimethylaminomethyl-2-oxo-1-cyclohexylmethylene)benzene dihydrochloride (3a) had lower IC(50) values than melphalan against the four cell lines and was 15 times more potent than this drug when examined against a panel of human tumours.
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: Amitabh
authors.initials: A
authors.lastname: Jha
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
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: Jennifer J
authors.initials: JJ
authors.lastname: Oucharek
authors.forename: Mohammed K
authors.initials: MK
authors.lastname: Pasha
authors.forename: Dallas
authors.initials: D
authors.lastname: Seitz
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Sharma
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 / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008352:Mannich Bases / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D008352:Mannich Bases