一种在大鼠中具有治疗活性的超氧化物歧化酶非肽类模拟物。

A nonpeptidyl mimic of superoxide dismutase with therapeutic activity in rats.

作者信息

Salvemini D, Wang Z Q, Zweier J L, Samouilov A, Macarthur H, Misko T P, Currie M G, Cuzzocrea S, Sikorski J A, Riley D P

机构信息

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

出版信息

Science. 1999 Oct 8;286(5438):304-6. doi: 10.1126/science.286.5438.304.

DOI:10.1126/science.286.5438.304

PMID:10514375

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.

摘要

许多人类疾病都与造成细胞损伤的氧自由基过量产生有关。一种含有双（环己基吡啶）取代大环配体的锰（II）配合物（M40403）被设计成超氧化物歧化酶（SOD）的功能模拟物，而超氧化物歧化酶通常能清除这些自由基。M40403具有较高的催化超氧化物歧化酶活性，且在体内具有化学和生物学稳定性。将M40403注射到炎症和缺血再灌注损伤的大鼠模型中，可保护动物免受组织损伤。这类模拟物可能会为超氧自由基介导的疾病带来更好的临床治疗方法。