Studies on the Development of Novel Anti-inflammatory Based on Superoxide Dismutase Activity

超氧化物歧化酶（SODs）催化超氧化物（O^-_）转化为过氧化氢和二氧。SOD提供了一种防御系统，抵御多种疾病，其中O^-_似乎起着重要作用，包括炎症、致癌和衰老。因此，测试SODs本身或作为药品的改性SODs是很重要的。有报道称，sod在临床环境中有有益的作用。然而，使用sod是困难的，因为它们很容易被肾脏清除，并且由于它们的高分子量而无法进入细胞。铜、锰和铁在SOD活性位点的存在使许多研究者寻找具有SOD活性的这些金属的低分子量配合物。虽然许多铜配合物在体外催化O^-_的畸变，但它们的反应活性在体内被活细胞中常见的螯合剂所减弱。有用的SOD模拟物应该能够跨越细胞膜，并且表现出稳定、活性和无毒。Fridovich和同事最近报道了Mn-desferal在体内作为SOD模拟物是有效的。很少有报道涉及含铁SOD模拟物。然而，与铜或锰相比，铁的毒性较低，这促使我们制备了具有亲脂性和中性配体的新型铁配合物。在本报告中，我们展示了铁(Il)-四合基-N，N，N‘，N’（2-吡啶基甲基）乙二胺（Fe- tpen）和铁(III)-三[N-（2-吡啶基甲基）-2-氨基乙基]胺（Fe- tpaa）的一些特性，它们具有高SOD活性，可以保护大肠杆菌细胞免受百草枯的毒性。此外，三[N-（3-甲基-2-吡啶甲基）-2-氨基乙基]胺（3MeTPAA）和三[（2-咪唑基）-2-氨基乙基]胺（TIAA）的铁配合物也被报道具有较高的SOD活性(conc。Fe- 3metpaa和Fe- tiaa的含量相当于1单位SOD (IC_<50>) = 0.5和1.0 muM)。这些新型复合物可能具有治疗用途。这些复合物的抗炎作用目前正在研究中。少

Superoxide dismutases (SODs) catalyze the conversion of superoxide (O^-_) to hydrogen peroxide plus dioxygen. SOD provides a defense system against several diseases in which O^-_ appears to play an important role, including inflammation, carcinogenesis and aging. It is therefore important to test SODs as such or modified SODs as pharmaceuticals. There have been reports of beneficial effects of SODs in clinical settings. It is difficult, however, to employ SODs because they are readily cleared by the kidney and are unable to enter cells because of their high molecular weight. The presence of copper, manganese, and iron at the active sites of SODs led many investigators to search for low molecular weight complexes of these metals having SOD activity. Although many copper complexes catalyze the dismutation of O^-_ in vitro, their reactivities are attenuated in vivo by chelating agents ordinarily found in living cells. Useful SOD mimics should be capable of crossing cell membranes and shou … More ld be stable, active and nontoxic. Fridovich and coworkers have recently reported that Mn-desferal is effective as an SOD mimic in vivo.Very little reported work deals with iron-containing SOD mimics. The low toxicity of iron in comparison with copper or manganese, however, led us to prepare novel iron complexes with lipophilic and neutral ligands.In this report, we show some of the properties of Fe(Il)-tetrakis-N,N,N',N'(2- pyridylmethyl)ethylenediamine (Fe-TPEN) and Fe(III)-tris[N-(2-pyridylmethyl)-2- aminoethyl]amine (Fe-TPAA) that have high SOD activity and can protect Escherichia coli cells from paraquat toxicity. In addition, both iron complexes of tris-[N-(3-methyl-2- pyridylmethy)-2-aminoethyl]amine (3MeTPAA) and tris[(2-imidazolyl)-2-aminoethyl]amine (TIAA) are also reported to have higher SOD activities (the conc. of Fe-3MeTPAA and Fe-TIAA equivalent to 1 unit of SOD (IC_<50>) = 0.5 and 1.0 muM, respectively) than other Fe and Cu complexes. These novel complexes may have therapeutic applications. The antiinflammatory effects of the complexes are now under investigation. Less