Novel 1,4 Substituted Piperidine Derivatives. Synthesis and Correlation of Antioxidant Activity with Structure and Lipophilicity

Abstract

Abstract A series of novel piperidine derivatives was prepared and their lipophilicity was determined (as RM values). These compounds as well as two intermediate α-keto-esters were tested for antioxidant activity. It was found that the cysteamine derivatives were efficient antioxidants, i.e. they could inhibit lipid peroxidation, act as hydroxyl radical scavengers and interact with 2,2-diphenyl-l-picrylhydrazyl radicals. This interaction could be attributed to the free SH group and this activity seemed to be favoured by increased lipophilicity. Replacement of SH by NH2 or OH resulted in a decreased antioxidant activity of the compounds. However, the described activities seem not to be connected with any O−2· scavenging ability, at least under the experimental conditions applied. Furthermore, cysteamine derivatives seem to induce O−2· generation, a phenomenon often observed with thiol compounds. The antioxidant activity of the intermediate α-keto-esters varied and is probably mediated by different mechanisms.