Design, Synthesis And Biological Evaluation Of Silybin Analogues

Silymarin, extracted from the fruits and the seeds of milk thistle Silybum marianum (L) Gaertn., consisted of a mixture of flavonolignans which were biosynthesized from the dihydroflavonol and phenylpropanoid derivatives. Previous studies have revealed that silymarin exhibited significant biological properties such as antioxidation, inhibition of lipid peroxidation and antihepatotoxic activity.Silybin, the main component of silymarin, has been reported possessing hepatoprotective activity as well as other interesting properties. During our investigation for better antioxidant and hepatoprotective agents, silybin was treated as a lead compound, therefore several series of silybin anologues were designed and synthesized. E-ring modified silybin anologues were synthesized via an efficient route. Furthermore, B-ring modified silybin anologues, 23-substituted silybin derivatives along with 7,20-substituted dihydrosilybin derivatives were prepared successfully. In summary, 94 compounds were synthesized by us. Among them, 60 compounds have not been reported by previous literature. Some synthetic compounds were evaluated for their superoxide anion radical activities and DPPH radical scavenging activities. Hence, the effects of the B- and E-ring substitute groups on the antioxidant activities were studied systematically. On the other hand, the cinnamic acid ethyl esters and the cinnamic alcohols, which were the intermediates of our syntheticprocedure, were evaluated for their xanthine oxidase inhibition activities. One of the compounds showed significant xanthine oxidase inhibitory activity, which was similar to that of the positive control allopurinol. The primary structure-activity relationship was further analyzed by us.The present studies afforded some useful information for further development of silybin analogues as novel hepatoprotective agents and cinnamic acid esters derivatives as xanthine oxidase inhibitors.