Multifunctional antioxidants for the treatment of age-related diseases

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 - Mar 1 2010

Fingerprint

Free Radical Scavengers
Antioxidants
Electrospray Ionization Mass Spectrometry
Sulfonamides
Macular Degeneration
Vitamin E
Astrocytes
Hydroxyl Radical
Cataract
Hydrogen Peroxide
Lenses
Glutathione
Cell Survival
Alzheimer Disease
Ions
Cell Line
Water

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Multifunctional antioxidants for the treatment of age-related diseases. / Jin, Hongxia; Randazzo, James; Zhang, Peng; Kador, Peter F.

In: Journal of Medicinal Chemistry, Vol. 53, No. 3, 01.03.2010, p. 1117-1127.

Research output: Contribution to journalArticle

Jin, Hongxia ; Randazzo, James ; Zhang, Peng ; Kador, Peter F. / Multifunctional antioxidants for the treatment of age-related diseases. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 3. pp. 1117-1127.
@article{d9581c1148e14204af0fa321349ae77f,
title = "Multifunctional antioxidants for the treatment of age-related diseases",
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).",
author = "Hongxia Jin and James Randazzo and Peng Zhang and Kador, {Peter F}",
year = "2010",
month = "3",
day = "1",
doi = "10.1021/jm901381j",
language = "English (US)",
volume = "53",
pages = "1117--1127",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "3",

}

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 - 2010/3/1

Y1 - 2010/3/1

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

VL - 53

SP - 1117

EP - 1127

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -