title: Affinity of vitamin E analogues for the ubiquinone complex II site correlates with their toxicity to cancer cells.
abstract: METHODS
  Vitamin E (VE) analogues, epitomised by the prototypic α-tocopheryl succinate (α-TOS), are potent anti-cancer agents. α-TOS has recently been shown to trigger apoptosis by targeting the ubiquinone (UbQ) binding site(s) of the mitochondrial complex II (CII) and to cause excessive production of reactive oxygen species.
  
  
  RESULTS
  We have modelled, using two approaches, a range of VE analogues into the proximal UbQ (Q(p) ) binding site of CII. This study reveals that in both cases, the calculated interaction energies of individual VE analogues correlate (R(2) value >0.8) with their toxicity to cancer cells.
  
  
  CONCLUSIONS
  These data further support the UbQ site(s) of CII as an important target determining the anti-cancer activity of VE analogues as well as other emerging anti-cancer drugs.
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD, Australia. j.neuzil@griffith.edu.au
authors.forename: Jiri
authors.initials: J
authors.lastname: Neuzil
authors.forename: Jiri
authors.initials: J
authors.lastname: Cerny
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Dyason
authors.forename: Lan-Feng
authors.initials: LF
authors.lastname: Dong
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ralph
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D042963:Electron Transport Complex II / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D014451:Ubiquinone; D014810:Vitamin E; D042963:Electron Transport Complex II