Thiazolidine carboxylic acid derivatives as antioxidant molecules; synthesis and evaluation

Oxidative stress that corresponds to a significant increase in free radical concentration in cells can cause considerable damage to crucial biological macromolecules if not prevented by cellular defense mechanisms. The low-molecular-weight thiol glutathione (GSH) constitutes one of the main intracellular antioxidants. It is synthesized via cysteine, an amino acid found only in limited amounts in cells because of its neurotoxicity. Thus, to ensure an efficient GSH synthesis in case of an oxidative stress, cysteine should be provided extracellularly. Yet, given its nucleophilic properties and its rapid conversion into cystine, its corresponding disulfide, cysteine is usually supplemented in a prodrug approach. In this study, the antioxidant properties of o, m or p substituted (2RS,4R)-2-phenyl-thiazolidine-4-carboxylic acid derivatives (1-12), heterocycles that potentially convert into cysteine in physiological conditions, were investigated. (2RS,4R)-2-phenyl-thiazolidine-4-carboxylic acid derivatives were synthesized by condensing L-cysteine with a series of mono or di substituted benzaldehydes. Compounds were characterized by LC-MS, FT-IR , 1H NMR, 13C NMR and elemental analisis. In vitro antioxidant properties were evaluated using the classical 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and by determining the cupric reducing antioxidant capacity (CUPRAC). Compounds are shown to exhibit relevant antioxidative properties that are not only attributed to cysteine release but also to the direct antioxidant capacity of the thiazolidine cycle itself.