Preparation of C-23 esterified silybin derivatives and evaluation of their lipid peroxidation inhibitory and DNA protective properties

A diverse series of C-23 esterified silybin derivatives (1a–n) were designed and synthesized. The antioxidative properties of these compounds were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide anion radical scavenging, ferrous ion chelation, and inhibition of rat liver homogenate lipid peroxidation. Their protective effects on the prevention of hydrogen peroxide induced DNA damage were also investigated. Most of the synthesized compounds exhibited more effective antioxidant activities than silybin. The esterified silybin analogues displayed satisfactory performance especially on iron chelation and antiperoxidative activity. Compound 1n in particular exhibited remarkable antiperoxidative effect with an IC₅₀ value of 0.2 ± 0.1 μM, which was stronger than that of quercetin (IC₅₀ = 1.8 ± 0.6 μM). Compounds 1c, 1e, 1g, 1h and 1k displayed potent, dose-dependent protective properties against DNA cleavage. The results of the bioassays support the antioxidative and DNA protective effects of these synthesized silybin derivatives.