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Science 8 October 1999:
Vol. 286. no. 5438, pp. 304 - 306
DOI: 10.1126/science.286.5438.304
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Reports

A Nonpeptidyl Mimic of Superoxide Dismutase with Therapeutic Activity in Rats

Daniela Salvemini, 1* Zhi-Qiang Wang, 2 Jay L. Zweier, 3 Alexandre Samouilov, 3 Heather Macarthur, 4 Thomas P. Misko, 2 Mark G. Currie, 2 Salvatore Cuzzocrea, 5 James A. Sikorski, 6 Dennis P. Riley 1

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.

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.
*   To whom correspondence should be addressed. E-mail: dsalvemini{at}metaphore.com

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