title: An acetate prodrug of a pyridinol-based vitamin E analogue.
abstract: OBJECTIVE
  To investigate of an approach to stabilize a novel pyridinol based α-tocopherol analogue (1) as a prodrug by acetylation of its phenol moiety.
  
  
  METHODS
  Biochemical indicators of oxidative stress in mitochondria were utilized to gain insight into the cytoprotective mechanism(s) of compound 1 acetate. Oxygen free radical scavenging activity was measured using DCF probe in a cultured cell model system that had been placed under oxidative stress. Lipid peroxidation was examined both in a cell-free system and in oxidatively stressed cultured cells. The bioenergetic parameters of mitochondria were evaluated by measuring mitochondrial membrane potential (Δψ(m)) and the MPT.
  
  
  RESULTS
  The present results suggest strongly that the antioxidant efficacy of compound 1 can be improved by using it as a prodrug. The tested prodrug has shown to be activated as a function of time, presumably due to susceptibility to enzymatic hydrolysis, and exhibits an antioxidant effect in time-dependent manner, providing a compound that is more effective than α-tocopherol acetate with regard to all protective properties studied.
  
  
  CONCLUSIONS
  An effective approach to stabilize compound 1 was realized by using its acetate as a prodrug.
authors: Biodesign Institute & Department of Chemistry & Biochemistry, Arizona State University, 1001 South McAllister Avenue, Tempe, Arizona 85287, USA.
authors: Omar M
authors: OM
authors: Khdour
authors: Jun
authors: J
authors: Lu
authors: Sidney M
authors: SM
authors: Hecht
mesh_terms: D000085:Acetates / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001896:Boron Compounds / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival; D002474:Cell-Free System; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015227:Lipid Peroxidation; D008081:Liposomes / Q000138:chemical synthesis* / Q000737:chemistry; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000085:Acetates; D000975:Antioxidants; D001896:Boron Compounds; D008081:Liposomes; D011355:Prodrugs; D017382:Reactive Oxygen Species; D014810:Vitamin E