Multifunctional antioxidants for the treatment of age-related diseases

Hongxia Jin, James Randazzo, Peng Zhang, Peter F. Kador

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Analogues of N,N-dimethyl-4-(pyrimidin-2-yl)piperazine-1-sulfonamide possessing a free radical scavenger group (FRS), chelating groups (CHL), or both (FRS + CHL) have been synthesized. Electrospray ionization mass spectrometry studies indicate that select members of this series bind ions in the relative order of Cu1+=Cu2+>Fe2+=Fe 3+>Zn2+ with no binding of Ca2+ or Mg 2+ observed. In vitro evaluation of these compounds in human lens epithelial, human retinal pigmented epithelial, and human hippocampal astrocyte cell lines indicates that all analogues possessing the FRS group as well as the water-soluble vitamin E analogue 6-hydroxy-2,5,7,8-tetramethylchroman-2- carboxylic acid protect these cells against decreased cell viability and glutathione levels induced by hydrogen peroxide. In addition, those compounds possessing CHL groups also protected these cells against hydroxyl radicals generated by the Fenton reaction. These compounds are good candidates for the preventive treatment of cataract, age-related macular degeneration (AMD), and Alzheimer's dementia (AD).

Original languageEnglish (US)
Pages (from-to)1117-1127
Number of pages11
JournalJournal of Medicinal Chemistry
Volume53
Issue number3
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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