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 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 26−1.6 μM. Carnosine-vanillin showed strong protection in the 833−104 μM range and some protection between 52−3.2 μM. Conversely, both sodium ascorbate and ascorbic acid did not protect DNA at any test concentration. In the pro-oxidant potential assessments, the synthesized antioxidants did not show any pro-oxidant effects at all concentrations, whereas sodium ascorbate showed severe pro-oxidant effects between 833−13 μM and ascorbic acid, 833−52 μM.Our study stresses the importance of ortho-methoxy group(s) for antioxidants as its electron-donating nature contributes to enhancing antioxidant activities, while steric bulk eliminates pro-oxidant effects by preventing the effective binding of transition metal ions to the phenolic hydroxyl group. The hydrophobicity of hindered phenols can be overcome if attached to a water-soluble scaffold.