Synthesis and evaluation of water-soluble antioxidants derived from l-carnosine and syringaldehyde (or vanillin).

Abstract

Polyphenols are well known for their health-related benefits, including antioxidant activities, but most of them are hydrophobic, decreasing their bioavailability. This study reports water-soluble trimeric antioxidants synthesized with l-carnosine and the hydrophobic ortho-methoxy-substituted phenolic unit, syringaldehyde or vanillin. In the DPPH assay, carnosine-syringaldehyde (7.5 μM) and carnosine-vanillin (19 μM) derivatives showed much lower IC50 values than ascorbic acid (27.5 μM) and sodium ascorbate (30.5 μM) standards. According to the AAPH assay, carnosine-syringaldehyde and carnosine-vanillin protect DNA at concentrations as low as 6.5 μM and 26 μM, respectively, while both sodium ascorbate and ascorbic acid protected until 52 μM. Another notable property of these antioxidants is that they can protect DNA well against hydroxyl radicals, produced via the Fenton reaction: carnosine-syringaldehyde showed DNA protection at all tested concentrations (833-1.6 μM), but the protection was slightly weaker between 26 and 1.6 μM. Carnosine-vanillin showed strong protection in the 833-104 μM range and some protection between 52 and 3.2 μM. Conversely, both sodium ascorbate and ascorbic acid did not protect DNA at any tested concentrations. In the pro-oxidant potential assessments, the synthesized antioxidants did not show any pro-oxidant effects at all tested concentrations. In comparison, sodium ascorbate at 833-13 μM and ascorbic acid at 833-52 μM both exhibited severe pro-oxidant effects. Our study highlights the significance of ortho-methoxy groups in antioxidants. Their electron-donating properties enhance antioxidant activities, while their steric bulk hinders the binding of transition metal ions to the phenolic hydroxyl group, thereby preventing pro-oxidant effects. The hydrophobicity of ortho-methoxy substituted phenols can be mitigated by attaching them to a highly water-soluble scaffold containing functional groups that can facilitate charge formation in the end products, such as carnosine.