Reactions of indole derivatives with cardioprotective activity with reactive oxygen species. Comparison with melatonin.
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.
Andreadou
Ioanna
I
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Zografou, Greece. ioannandread@yahoo.com
Tsantili-Kakoulidou
Anna
A
Spyropoulou
Eleni
E
Siatra
Theodora
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D005609:Free Radicals / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008550:Melatonin / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
D000975:Antioxidants; D002316:Cardiotonic Agents; D005609:Free Radicals; D007211:Indoles; D017382:Reactive Oxygen Species; D008550:Melatonin