Synthesis and biological evaluation of scutellarein alkyl derivatives as preventing neurodegenerative agents with improved lipid soluble properties.

Background: Exogenous antioxidants are considered as a promising therapeutic approach to treat neurodegenerative diseases, since they could prevent and/or minimize the neuronal damage by oxidation. Objective: Three series of lipophilic compounds structurally based on scutellarein (2), which is one metabolite of scutellarin (1) in vivo, have been designed and synthesized. Method: Their antioxidant activity was evaluated by detecting the 2-thiobarbituric acid reactive substance (TBARS) produced in the ferrous salt/ascorbate induced autoxidation of lipids, which were present in microsomal membranes of rat hepatocytes. The lipophilicity of these compounds indicated as partition coefficient between n-octanol and buffer was investigated by ultraviolet (UV) spectrophotometer. Results: This study indicated that compound 5e which had a benzyl group substituted at the C4';-OH position showed a potent antioxidant activity and good lipophilicity. Conclusion: 5e could be effective candidate for preventing or reducing the oxidative status associated with the neurodegenerative processes.