TY - JOUR
T1 - Multifunctional antioxidants for the treatment of age-related diseases
AU - Jin, Hongxia
AU - Randazzo, James
AU - Zhang, Peng
AU - Kador, Peter F.
PY - 2010
Y1 - 2010
N2 - 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).
AB - 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).
UR - http://www.scopus.com/inward/record.url?scp=77249087164&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77249087164&partnerID=8YFLogxK
U2 - 10.1021/jm901381j
DO - 10.1021/jm901381j
M3 - Article
C2 - 20078105
AN - SCOPUS:77249087164
SN - 0022-2623
VL - 53
SP - 1117
EP - 1127
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 3
ER -