Characterisation of novel indenoindoles. Part II. Redox-recycling with ascorbate

Abstract

In the accompanying paper it was shown that the new antioxidant, H 290/51 (cis-5,5a,6,10b-tetrahydro-9-methoxy-7-methylindeno [2,1-b]indole), is a powerful antioxidant in several pharmacological models of lipid peroxidation and could be useful as a therapeutic agent in pathophysiological situations where lipid peroxidation plays an important role. In the present study, we characterised H 290/51 as an inhibitor of peroxidation of pure methyl linoleate. H 290/51 almost completely inhibited peroxidation induced by a lipid-soluble initiator at 37 °C during the induction period, both in an aqueous solution of micelles in the presence of detergents and in a homogeneous ethanol solution. In both systems, the time of the induction period was linearly related to the concentration of H 290/51. In the ethanol solution, ascorbic acid had a sparing effect on H 290/51, indicating effective interference with radical chain propagation. In aqueous solution with micelles of methyl linoleate made with the nonionic detergents Triton X-100 or Lubrol PX, ascorbic acid did not inhibit peroxidation. However, in these micelles, H 290/51 showed a concentration-dependent extension of the induction period by ascorbic acid, suggesting recycling. In the presence of the zwitterionic detergent CHAPS, although a clear induction period is seen with H 290/51, no recycling by ascorbic acid was found. The ability of H 290/51 to recycle in aqueous solutions, thus depends on the micellar composition.