INFLUENCE OF STRUCTURE ON THE ANTIOXIDANT ACTIVITY OF INDOLINIC NITROXIDE RADICALS

An in vitro study was carried out to verify whether the chain length o f a substituent on an indolinic nitroxide could influence its antioxid ant activity in different biological environments subjected to oxidati ve stress. Three distinct indolinic nitroxides were synthesized and co mpared with vitamin E and Trolox (a hydrophilic analogue of vitamin E) , where the only difference between the nitroxides was the length of t he hydrocarbon chain in the 2-position of indole, namely 2 (C2), 10 (C 10), and 18 (C18) carbons. All the nitroxides were effective in preven ting oxidation of bovine serum albumin, but to different extents, with the longer chain derivatives being more efficient. However, the C2 co mpound was the most efficient in preventing lipid peroxidation in micr osomal membranes. The C2 and C18 compounds, Trolox, and vitamin E prot ected microsomal protein oxidation to the same extent at the highest c oncentration used (13 mu M). The nitroxide with a C10 chain was less e ffective in this system. The influence of these compounds on the enzym atic activity of two mitochondrial proteins subjected to oxidative str ess was also studied by means of oxygraph measurements. Mitochondrial rotenone-sensitive NADH oxidase and succinate oxidase responded differ ently to Bu(t)OOH-induced radical chemistry, and the compounds under s tudy also protected the activity of the two enzymes but to different e xtents. The results clearly demonstrate that indolinic nitroxides are very efficient antioxidants, protecting both lipids and proteins from peroxidation. The indole structure influences the antioxidant efficacy in biological systems. Copyright (C) 1996 Elsevier Science Inc.