Synthesis and Biological Activity of Lipoic Acid Ester Derivatives

A series of lipoic acid derivatives was synthesized via the modification of carboxyl groups of lipoic acid, 23 target compounds were obtained and characterized by nuclear magnetic resonance and high resolution mass spectrometry. Lipoic acid derivatives were employed in order to explore the potential structure. antioxidant activity relationships. The antioxidant activities of these compounds were evaluated and compared by the acrolein assay, 1,1-diphenyl-2-picrylhydrazyl(DPPH) assay, 2,2'-azino. bis(3-ethylbenzothiazoline-6-sul. phonic acid) diammonium(ABTS) assay and ferric reducing antioxidant power(FRAP) assay. Acrolein scavenging activity test results showed that most compounds exhibited acrolein scavenging activities, compounds 3a, 3b, 3e, 3f, 3k, 3m, 3q, 3v and 3w had good acrolein scavenging activities, especially compound 3a showed the highest acrolein scavenging activity which was stronger than carnosine. The experimental results showed that most compounds exhibited DPPH scavenging activities, compounds 3o, 3p, 3v and 3w had good DPPH scavenging activities, especially compound 3w showed the highest DPPH scavenging activity, which was close to 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid(Trolox) and Vitamin C. The results showed that most compounds exhibited ABTS scavenging activities, compounds 3b, 3e, 3u, 3v and 3w had good ABTS scavenging activities, especially compound 3w showed the highest ABTS scavenging activity, which was very close to trolox and Vitamin C. FRAP experimental results showed that most compounds exhibited reduction activities to ferricion-2,4,6-tri(2-pyridyl)-s-triazine(Fe3+-TPTZ) complex, compounds 3b, 3v and 3w had good reduction activities to Fe3+-TPTZ complex, especially compound 3w showed the highest reduction activity to Fe3+-TPTZ complex, which was stronger than Vitamin C and trolox. The results showed that most compounds exhibited hydroxyl radical scavenging activities, compounds 3j and 3w had good hydroxyl radical scavenging activities, especially compound 3w showed the highest hydroxyl radical scavenging activity which was stronger than trolox-Plasma stability assay results showed that compared with lipoic acid, twenty-three compounds had good plasma stability.