2-(Aminomethyl)chromans That Inhibit Iron-Dependent Lipid Peroxidation and Protect against Central Nervous System Trauma and Ischemia

E. Jon Jacobsen, Donald E. Ayer, Kenneth L. Belongs, J. Mark Braughler, Edward D. Hall, David J. Houser, Fred J. VanDoornik

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

A series of 2-(aminomethyl)chromans was developed as potent inhibitors of iron-dependent lipid peroxidation. Compounds within this class are extremely effective at inhibiting lipid peroxidation with IC50's as low as 0.2 μM. Selected members were found to enhance early neurological recovery and survival in a mouse head injury model. In this assay, improvement in the 1-h post-head-injury neurological status (grip test score) by as much as 230% of control was observed. One of the most efficacious compounds (35) was evaluated in two models of cerebral ischemia where significant neuroprotection was observed. These results provide further support for the importance of cerebroprotective antioxidants for the treatment of traumatic and ischemic injury as well as additional evidence for the role of oxygen radicals in postischemic brain damage.

Original languageEnglish
Pages (from-to)4464-4472
Number of pages9
JournalJournal of Medicinal Chemistry
Volume35
Issue number23
DOIs
StatePublished - Nov 1 1992

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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