The pyrrolopyrimidine U101033E is a potent free radical scavenger and prevents Fe(II)-induced lipid peroxidation in synaptosomal membranes

Christopher M. Lauderback, Adam M. Breier, Janna Hackett, Sridhar Varadarajan, Jessica Goodlett-Mercer, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The pyrrolopyrimidine U101033E is a therapeutic compound potentially useful in stroke, head injury and other oxidative stress conditions. Electron paramagnetic resonance (EPR) techniques of spin labeling and spin trapping in conjunction with measures of lipid and protein oxidation have been used to investigate the proposed antioxidant capacity of U101033E. We report potent antioxidant activity of this agent in aqueous cell-free solution as measured by spin trapping. U101033E significantly (P<0.005) reduces the formation of the EPR active spin trap N-t-butyl-α-phenylnitrone (PBN)-radical adduct by 17.1% at a concentration of 1 μM, four orders of magnitude less than the concentration of PBN. As measured by the decrease in signal intensity of lipid-resident nitroxide stearate spin probes, an EPR assay for lipid peroxidation, this pyrrolopyrimidine compound efficiently protected against hydroxyl radical-induced lipid peroxidation in cortical synaptosomal membranes deep within the membrane bilayer, but not closer to the membrane surface. In addition, U101033E partially prevents synaptosomal protein oxidation in the presence of Fe(II); however, U101033E demonstrates some protein oxidative effects itself. These results are supportive of the proposed role of U101033E as a lipid-specific antioxidant, especially for protection against lipid peroxidation that occurs deep within the membrane bilayer, but raise some potential concerns about the oxidative nature of this agent toward proteins. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)149-161
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number2-3
StatePublished - Jun 15 2000

Bibliographical note

Funding Information:
This work was supported in part by grants from NIH (AG-05119; AG-10836) and NSF (CHE-9531406).


  • Antioxidant
  • Electron paramagnetic resonance
  • Lipid peroxidation
  • Oxidative stress
  • Pyrrolopyrimidine
  • Spin trapping

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology


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