title: Dimeric 3,5-bis(benzylidene)-4-piperidones: a novel cluster of tumour-selective cytotoxins possessing multidrug-resistant properties.
abstract: A series of bis[3,5-bis(benzylidene)-4-oxo-1-piperidinyl]amides 1 display potent cytotoxic properties towards a wide range of tumours. A number of the CC(50) and IC(50) values are in the range of 10(-8) M. Specifically, these compounds have the following important properties. First, greater toxicity was demonstrated towards certain tumours than various non-malignant cells. Second, various compounds in series 1 are toxic to a number of human colon cancer and leukaemic cells. Third, these compounds reverse P-gp mediated multidrug resistance. Various prototypic molecules such as 1a,b and 1i were identified as lead molecules for further studies. A representative lead molecule 1b induces apoptosis via internucleosomal DNA fragmentation and PARP cleavage in HSC-2 and HL-60 cells while flow cytometry revealed that this compound blocked the G2/M and S-phases in the cell cycle of human colon cancer HCT-116 cells.
authors.affiliation: Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
authors.forename: Swagatika
authors.initials: S
authors.lastname: Das
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
authors.forename: Naoki
authors.initials: N
authors.lastname: Umemura
authors.forename: Shoko
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Matsuta
authors.forename: Masami
authors.initials: M
authors.lastname: Kawase
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnár
authors.forename: Julianna
authors.initials: J
authors.lastname: Serly
authors.forename: Dennis K J
authors.initials: DK
authors.lastname: Gorecki
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D010881:Piperidones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C526290:3,5-bis(benzylidene)-4-piperidone; D000970:Antineoplastic Agents; D010881:Piperidones