SYNTHESIS AND CHARACTERIZATION OF NEW SILIBININ PHOSPHODIESTER CONJUGATES: EXPLORING THEIR PROPERTIES.

Polyphenols are active compounds from medicinal plants widely distributed in nature. Many reports suggest that the mechanisms by which plant polyphenols exert their protective actions against various diseases are in part due to their redox properties [1]. Silibinin, belonging to flavonolignan class, is the major component of Silymarin complex extracted from the fruits of milk thistle (Silybum marianum) [2]. Silibinin is a diastereoisomeric mixture of two flavonolignans, Silybin A and Silybin B, in a ratio of approximately 1:1; this metabolite has long been studied for its large variety of pharmacological properties ranging from the antioxidant to neuroprotective [3] and antiviral activities. Unfortunately, many drug candidates including Silibinin, even if have been reported to possess a strong therapeutic potential in vitro, fail in vivo because of their poor bioavailability, often connected to a low water solubility. The design and synthesis of water-soluble pro-drugs are a powerful approach in order to overcome these limits and to improve the pharmacological potentialities of these compounds [4]. In this regard, here, we report the synthesis and characterization of new phosphodiester Silibinin conjugates by the insertion of a phosphate group at the 9” position. This, besides improving the Silibinin water solubility, allows conjugation of different molecules (Figure) able to recognize cell targets and to improve Silibinin pharmaceutical properties [5-8]. The new derivatives have been tested in different radical scavenging assays. A antiviral and neuroprotective activities have also been explored.