Silybinin and silybins: purification, new molecules and evaluation of antioxidant properties

Flavonoids and flavonolignans are widely distributed among various citrus plants and are frequently found in the human diet. They exhibit a variety of properties, such as enzyme inhibitor, free radical scavenger, antitumor agent, antibacterial, antiinflammatory and antioxidant. Flavonolignan silibinin is the major component (ca. 30%) of the silymarin complex extracted from the seeds of Silybum marianum, with multiple biological activities operating at various cell levels. Silibinin and the other silymarin flavonolignans (isosilybin, silychristin, and silydianin) are biogenetically formed by the oxidative (radical) coupling of coniferyl alcohol to the catechol moiety of taxifolin. This reaction is not stereospecific, and thus all respective flavonolignans occur in the silymarin complex in diastereomeric pairs in proportions of ca. 1:1. Along with the beneficial activities resulting from the antioxidant and radical scavenging properties, recently silibinin has received attention due to its anticancer and chemopreventive actions, as well as hypocholesterolemic, cardioprotective, and neuroprotective activities. Silybin are rather hampered by its very low bioavailability. In an attempt to improve its biological properties and facilitate in vivo applications of silibinin, only few structural modifications have been proposed and the available analogues are still unsatisfactory, therefore new synthetic approaches for selectively modifying silibinin are of high interest. As a part of our continuing research effort towards the synthesis of new natural product analogues, we present here the preliminary results of a efficient synthetic procedure to obtain new modified silibinin derivatives. The antioxidant properties of the new compounds has been evaluated in a cellular model in vivo.