A Nonpeptidyl Mimic of Superoxide Dismutase with Therapeutic Activity in Rats-Reference-Cited by-同舟云学术

A Nonpeptidyl Mimic of Superoxide Dismutase with Therapeutic Activity in Rats

Published:1999-10-08 Issue:5438 Volume:286 Page:304-306
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Salvemini Daniela¹,Wang Zhi-Qiang²,Zweier Jay L.³,Samouilov Alexandre³,Macarthur Heather⁴,Misko Thomas P.²,Currie Mark G.²,Cuzzocrea Salvatore⁵,Sikorski James A.⁶,Riley Dennis P.¹

Affiliation:

1. MetaPhore Pharmaceuticals, 1910 Innerbelt Business Center Drive, St. Louis, MO 63114, USA.

2. Discovery Pharmacology, G. D. Searle, Monsanto Company, 800 North Lindbergh Boulevard, St. Louis, MO 63167, USA.

3. Electron Paramagnetic Resonance Center, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.

4. Department of Pharmacological and Physiological Sciences, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.

5. Institute of Pharmacology, School of Medicine, University of Mesiina, Piazza XX Settembre nb 4, 98123 Messina, Italy.

6. Discovery Medicinal Chemistry, G. D. Searle, Monsanto Company, Chesterfield Village Parkway, St. Louis, MO 63198, USA.

Abstract

Many human diseases are associated with the overproduction of oxygen free radicals that inflict cell damage. A manganese(II) complex with a bis(cyclohexylpyridine)-substituted macrocyclic ligand (M40403) was designed to be a functional mimic of the superoxide dismutase (SOD) enzymes that normally remove these radicals. M40403 had high catalytic SOD activity and was chemically and biologically stable in vivo. Injection of M40403 into rat models of inflammation and ischemia-reperfusion injury protected the animals against tissue damage. Such mimics may result in better clinical therapies for diseases mediated by superoxide radicals.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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