title: Cytotoxic evaluation of some N-acyl and N-acyloxy analogues of 3,5-bis(arylidene)-4-piperidones.
abstract: The preparation of thirteen N-acyl and N-acyloxy analogues of two 3,5-bis(arylidene)-4-piperidones were prepared as potential prodrugs of the parent ketones. Approximately half of the compounds demonstrated antileukemic properties when evaluated against murine L1210 lymphoid leukemia cells. Three of the derivatives were more active than or equipotent with the reference drug melphalan. All of the compounds were examined against approximately 55 human tumours representing eight different neoplastic diseases. Not only were most of the compounds more cytotoxic than melphalan but 60% of the derivatives displayed selective toxicity to leukemia. A stability study of six of the candidate prodrugs using 1H NMR spectroscopy revealed that while some decomposition in solution occurred, the parent amine was not liberated.
authors.affiliation: College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Dimmock
authors.forename: V K
authors.initials: VK
authors.lastname: Arora
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: T M
authors.initials: TM
authors.lastname: Allen
authors.forename: G Y
authors.initials: GY
authors.lastname: Kao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity*; D002462:Cell Membrane / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010881:Piperidones / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity*; D011355:Prodrugs / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010881:Piperidones; D011355:Prodrugs