Scavenging of reactive oxygen species by N-substituted indole-2 and 3-carboxamides

Abstract

Indole-2 and 3-carboxamides (IDs) are proposed to be selective cyclooxygenase inhibitors. Since cyclooxygenase-1 may be involved in reactive oxygen species (ROS) production, we hypothesize that these indole derivatives have antioxidative properties. We have employed chemiluminescence (CL) and electron spin resonance (ESR) spin trapping to examine this hypothesis. We report here the results of a study of reactivity of 10 selected indole derivatives towards ROS. The following generators of ROS were applied: potassium superoxide (KO2) as a source of superoxide radicals (O2 (.-)), the Fenton reaction (Co-EDTA/H2O2) for hydroxyl radicals (HO.), and a mixture of alkaline aqueous H2O2 and acetonitrile for singlet oxygen (1O2). Hydroxyl radicals were detected as 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin adduct, whereas 2,2,6,6-tetramethyl-piperidine (TEMP) was used as a detector of 1O2. Using the Fenton reaction, 0.5 mmol/L IDs were found to inhibit DMPO-.OH radical formation in the range 7-37%. Furthermore the tested compounds containing the thiazolyl group also inhibited the 1O2-dependent TEMPO radical, generated in the acetonitrile + H2O2 system. About 20% inhibition was obtained in the presence of 0.5 mmol/L IDs. 1 mmol/L IDs caused an approximately 13-70% decrease in the CL sum from the O2 (.-) generating system (1 mmol/L). The aim of this paper is to evaluate these indole derivatives as antioxidants and their abilities to scavenge ROS.