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

doi:10.1021/jm00101a025

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

40 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 language	English
Pages (from-to)	4464-4472
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	35
Issue number	23
DOIs	https://doi.org/10.1021/jm00101a025
State	Published - Nov 1 1992

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm00101a025

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

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.",

author = "Jacobsen, {E. Jon} and Ayer, {Donald E.} and Belongs, {Kenneth L.} and Braughler, {J. Mark} and Hall, {Edward D.} and Houser, {David J.} and VanDoornik, {Fred J.}",

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T1 - 2-(Aminomethyl)chromans That Inhibit Iron-Dependent Lipid Peroxidation and Protect against Central Nervous System Trauma and Ischemia

AU - Jacobsen, E. Jon

AU - Ayer, Donald E.

AU - Belongs, Kenneth L.

AU - Braughler, J. Mark

AU - Hall, Edward D.

AU - Houser, David J.

AU - VanDoornik, Fred J.

PY - 1992/11/1

Y1 - 1992/11/1

N2 - 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.

AB - 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.

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

Abstract

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