title: Design, synthesis and cytotoxic properties of novel 1-[4-(2-alkylaminoethoxy)phenylcarbonyl]-3,5-bis(arylidene)-4-piperidones and related compounds.
abstract: The 3,5-bis(arylidene)-4-piperidones 1 contain the 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore which is considered to interact at a complementary binding site in susceptible neoplasms. The hypothesis was formulated that the presence of an acyl group attached to the piperidyl nitrogen atom in series 1 may interact with an additional binding site thereby enhancing cytotoxic potencies. This concept led to the synthesis of various N-acyl-3,5-bis(arylidene)-4-piperidones 3-7 many of which displayed significant cytotoxicity towards a variety of cancer cell lines. A comparison of the potencies between the compounds in series 1 and the related nonquaternary analogues 3-6 revealed that in approximately half of the comparisons made, the N-acyl analogues had increased potencies.
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Crescent, Saskatoon, Saskatchewan S7N 5C9, Canada.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Jane
authors.initials: J
authors.lastname: Alcorn
authors.forename: Anuraag
authors.initials: A
authors.lastname: Shrivastav
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Sharma
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010881:Piperidones