Andreadou Ioanna, Tsantili-Kakoulidou Anna, Spyropoulou Eleni, Siatra Theodora
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Zografou, Greece.
Chem Pharm Bull (Tokyo). 2003 Oct;51(10):1128-31. doi: 10.1248/cpb.51.1128.
We have previously reported on the synthesis of novel indole derivatives containing an amine-triazole moiety (1a-d, 2a-c), and their antioxidant activity on in vitro non-enzymatic rat hepatic microsomal lipid peroxidation. Some of the compounds showed protective activity against oxidative injury of ischemic myocardium. In the present paper we investigated the interactions of these derivatives with reactive oxygen species, in order to find a mechanism of their antioxidant capacity and to identify structural characteristics responsible for these properties. These interactions were compared with melatonin, which is also an indole derivative. The antioxidant profiles of the compounds were established by different in vitro protocols as follows: 1) by the interaction of the compounds with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable free radical, 2) their scavenging effects on superoxide anions using an enzymic system of xanthine-xanthine oxidase, 3) their inhibitory effects on xanthine oxidase and 4) their ability to scavenge hydroxyl radicals by comparison with dimethyl sulfoxide (DMSO) for *OH. All compounds were found to interact with DPPH, most of them to be superoxide anion scavengers and to be strong hydroxyl radical scavengers. Derivatives 1a and 1d substituted on the nitrogen of the indolic nucleus were found to have better antioxidant properties than the reference compounds used and melatonin.
我们之前报道过含胺 - 三唑部分的新型吲哚衍生物（1a - d，2a - c）的合成，以及它们对体外非酶促大鼠肝微粒体脂质过氧化的抗氧化活性。一些化合物对缺血性心肌的氧化损伤表现出保护活性。在本文中，我们研究了这些衍生物与活性氧的相互作用，以找出其抗氧化能力的机制，并确定导致这些性质的结构特征。将这些相互作用与同样是吲哚衍生物的褪黑素进行了比较。通过以下不同的体外实验方案确定了化合物的抗氧化谱：1）通过化合物与1,1 - 二苯基 - 2 - 苦基肼基（DPPH）稳定自由基的相互作用；2）使用黄嘌呤 - 黄嘌呤氧化酶酶系统对超氧阴离子的清除作用；3）它们对黄嘌呤氧化酶的抑制作用；4）与二甲基亚砜（DMSO）相比，它们清除羟基自由基的能力。发现所有化合物都与DPPH相互作用，其中大多数是超氧阴离子清除剂，并且是强羟基自由基清除剂。发现在吲哚核氮原子上被取代的衍生物1a和1d比所使用的参考化合物和褪黑素具有更好的抗氧化性能。
