Synthesis of new lipoic acid conjugates and evaluation of their free radical scavenging and neuroprotective activities

Abstract

A series of new lipoic acid derivatives were designed and synthesized as multitarget ligands against Alzheimer's disease. In particular, analogues combining both lipoic acid and cysteine core structures were synthesized. The antioxidant properties of these compounds were evaluated by 1,1-diphenyl-2- picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) radical cation scavenging assays and ferrous ion chelation. The antioxidant potential of the synthesized compounds was also evaluated in a cellular context and compared to α-lipoic acid and its reduced form, dihydrolipoic acid. The antioxidant effects observed for these compounds in vitro confirmed the importance of free thiol functions for effective antioxidant capacities. However, these promising in vitro results were not mirrored by the antioxidant activity in T67 cell line. This suggests that multiple factors are at stake and warrant further investigations. A series of new lipoic acid derivatives have been synthesized and evaluated for their potential antioxidant and neuroprotective activities. Structure-activity relationship studies comparing lipoic acid derivatives and their corresponding reduced analogues revealed the importance of free thiol functions. © 2014 John Wiley & Sons A/S.