Work

Multifunctional Antioxidants for the Treatment of Age-Related Diseases

Year: 2010

Type: article

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 Cu(1+) = Cu(2+) > Fe(2+) = Fe(3+) > Zn(2+) with no binding of Ca(2+) 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).

Source: Journal of Medicinal Chemistry

DOI: 10.1021/jm901381j

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

Institution: University of Nebraska Medical Center

Language: English

Topic: Free Radicals and Antioxidants

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Eye Institute