An acetate prodrug of a pyridinol-based vitamin e analogue

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14 Scopus citations

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)2896-2909
Number of pages14
JournalPharmaceutical Research
Volume28
Issue number11
DOIs
StatePublished - Nov 1 2011

Keywords

  • Analogue
  • Antioxidant
  • Prodrug
  • Pyridinol
  • Reactive oxygen species (ROS)
  • Stability
  • α-tocopherol acetate

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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