A novel anti-oxidant and anti-cancer strategy: a peptoid anti-inflammatory drug conjugate with SOD mimic activity

M.A. Bailey, Matthew Ingram, D.P. Naughton

Research output: Contribution to journalArticle

Abstract

Activation of reactive oxygen and nitrogen species (RONS) by redox-active metal ions has been proposed to contribute to oxidative damage in inflamed tissues. Here, we report a dual-function anti-oxidant conjugate comprising an anti-inflammatory agent (5-aminosalicylic acid) and a chelator with potential as a superoxide dismutase mimic. The conjugate ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) [EBAME] chelates Cu(II) ions in a 1:1 ratio, as assessed spectrophotometrically using Job’s method. Superoxide dismutase (SOD) activity was determined for the Mn(II)-conjugate as 0.758 ± 0.130 U at a concentration of 0.99 μM. In inflamed tissues, peptidase mediated release of active 5-ASA would also release the EDTA chelator which has significant SOD mimic activity when complexed to Cu(II) ions. Thus, EBAME has potential as a dual-function anti-inflammatory agent with reduced gastric irritability.
Original languageEnglish
Pages (from-to)1155-1158
Number of pages4
JournalBiochemical and biophysical research communications
Volume317
Issue number4
DOIs
Publication statusPublished - May 2004

Fingerprint

Peptoids
Oxidants
Superoxide Dismutase
Mesalamine
Anti-Inflammatory Agents
Chelating Agents
Edetic Acid
Pharmaceutical Preparations
Ions
Tissue
Reactive Nitrogen Species
Metal ions
Reactive Oxygen Species
Esters
Peptide Hydrolases
Chemical activation

Keywords

  • Superoxide dismutase mimic
  • 5-Aminosalicylic acid
  • Ethylenediaminetetraacetic acid
  • Metal ions
  • Inflammation

Cite this

@article{cd74309d2b5f47d684e1724ca6c489f3,
title = "A novel anti-oxidant and anti-cancer strategy: a peptoid anti-inflammatory drug conjugate with SOD mimic activity",
abstract = "Activation of reactive oxygen and nitrogen species (RONS) by redox-active metal ions has been proposed to contribute to oxidative damage in inflamed tissues. Here, we report a dual-function anti-oxidant conjugate comprising an anti-inflammatory agent (5-aminosalicylic acid) and a chelator with potential as a superoxide dismutase mimic. The conjugate ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) [EBAME] chelates Cu(II) ions in a 1:1 ratio, as assessed spectrophotometrically using Job’s method. Superoxide dismutase (SOD) activity was determined for the Mn(II)-conjugate as 0.758 ± 0.130 U at a concentration of 0.99 μM. In inflamed tissues, peptidase mediated release of active 5-ASA would also release the EDTA chelator which has significant SOD mimic activity when complexed to Cu(II) ions. Thus, EBAME has potential as a dual-function anti-inflammatory agent with reduced gastric irritability.",
keywords = "Superoxide dismutase mimic, 5-Aminosalicylic acid, Ethylenediaminetetraacetic acid, Metal ions, Inflammation",
author = "M.A. Bailey and Matthew Ingram and D.P. Naughton",
year = "2004",
month = "5",
doi = "10.1016/j.bbrc.2004.03.162",
language = "English",
volume = "317",
pages = "1155--1158",
journal = "Biochemical and biophysical research communications",
issn = "0006-291X",
number = "4",

}

A novel anti-oxidant and anti-cancer strategy: a peptoid anti-inflammatory drug conjugate with SOD mimic activity. / Bailey, M.A.; Ingram, Matthew; Naughton, D.P.

In: Biochemical and biophysical research communications, Vol. 317, No. 4, 05.2004, p. 1155-1158.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A novel anti-oxidant and anti-cancer strategy: a peptoid anti-inflammatory drug conjugate with SOD mimic activity

AU - Bailey, M.A.

AU - Ingram, Matthew

AU - Naughton, D.P.

PY - 2004/5

Y1 - 2004/5

N2 - Activation of reactive oxygen and nitrogen species (RONS) by redox-active metal ions has been proposed to contribute to oxidative damage in inflamed tissues. Here, we report a dual-function anti-oxidant conjugate comprising an anti-inflammatory agent (5-aminosalicylic acid) and a chelator with potential as a superoxide dismutase mimic. The conjugate ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) [EBAME] chelates Cu(II) ions in a 1:1 ratio, as assessed spectrophotometrically using Job’s method. Superoxide dismutase (SOD) activity was determined for the Mn(II)-conjugate as 0.758 ± 0.130 U at a concentration of 0.99 μM. In inflamed tissues, peptidase mediated release of active 5-ASA would also release the EDTA chelator which has significant SOD mimic activity when complexed to Cu(II) ions. Thus, EBAME has potential as a dual-function anti-inflammatory agent with reduced gastric irritability.

AB - Activation of reactive oxygen and nitrogen species (RONS) by redox-active metal ions has been proposed to contribute to oxidative damage in inflamed tissues. Here, we report a dual-function anti-oxidant conjugate comprising an anti-inflammatory agent (5-aminosalicylic acid) and a chelator with potential as a superoxide dismutase mimic. The conjugate ethylenediaminetetraacetic acid bis-(5-aminosalicylic acid methyl ester) [EBAME] chelates Cu(II) ions in a 1:1 ratio, as assessed spectrophotometrically using Job’s method. Superoxide dismutase (SOD) activity was determined for the Mn(II)-conjugate as 0.758 ± 0.130 U at a concentration of 0.99 μM. In inflamed tissues, peptidase mediated release of active 5-ASA would also release the EDTA chelator which has significant SOD mimic activity when complexed to Cu(II) ions. Thus, EBAME has potential as a dual-function anti-inflammatory agent with reduced gastric irritability.

KW - Superoxide dismutase mimic

KW - 5-Aminosalicylic acid

KW - Ethylenediaminetetraacetic acid

KW - Metal ions

KW - Inflammation

U2 - 10.1016/j.bbrc.2004.03.162

DO - 10.1016/j.bbrc.2004.03.162

M3 - Article

VL - 317

SP - 1155

EP - 1158

JO - Biochemical and biophysical research communications

JF - Biochemical and biophysical research communications

SN - 0006-291X

IS - 4

ER -