A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats.
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.
Salvemini
D
D
MetaPhore Pharmaceuticals, 1910 Innerbelt Business Center Drive, St. Louis, MO 63114, USA. dsalvemini@metaphore.com
Wang
Z Q
ZQ
Zweier
J L
JL
Samouilov
A
A
Macarthur
H
H
Misko
T P
TP
Currie
M G
MG
Cuzzocrea
S
S
Sikorski
J A
JA
Riley
D P
DP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D019610:Cytoprotection; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004355:Drug Stability; D007249:Inflammation / Q000188:drug therapy*; D007375:Interleukin-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008345:Manganese; D018716:Molecular Mimicry; D009504:Neutrophils / Q000187:drug effects; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013152:Splanchnic Circulation; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D009942:Organometallic Compounds; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C121876:imisopasem manganese; D008345:Manganese; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D015232:Dinoprostone