1. The project of the Czechoslovak Academy of Sciences Institute of Microbiology in Prague concerns the preparation of glycosylated derivatives of silymarins for improving the solubility and the drug targetting of this compound.
Silymarin acts as a radical scavenger, as an anti-lipid peroxidant and it modulates the fluidity of cell membranes of hepatocytes. Its therapeutic effect however, is hampered by its low solubility and should be enhanced by increasing the solubility. Its hepatotropic properties should be improved by attaching specific glycosidic regidues to the molecule. The proposal is that dr. Kren in Prague synthesizes the silymarin glycoside derivatives. These compounds will than be tested in the laboratories of Meijer in Groningen, Reichen in Berne and Jansen in Groningen in whole animals isolated perfused normal livers (Meijer), and isolated perfused cirrhotic livers (Reichen). Jansen will test the effect of these compounds on hepatic transport processes using the BIOMED core facility of the CSLM in Groningen. Reichen will test whether these improved compounds will prevent liver cirrhosis in the CCl4 model and the model of biliary cirrhosis.
2. The project of the Latvian Institute of Organic Synthesis in Riga, Latvia, deals with the the synthesis of a novel class of antioxidants and membrane protectors, derivatives of 1,4-dihydropyridine (1,4-DHP). These compounds will be used as antioxidants, as membranoprotectors, as fluorescent probes and as inhibitors of protein kinase cAMP. In a very similar set up as in proposal 1, the Latvian Institute will synthesize these compounds, which than will be tested in the laboratories of Meijer (Groningen), Reichen (Berne) and Jansen (Groningen). The Biomed core facility, the CSLM in Groningen, will also be employed in this proposal. It offers the excellent possibility to study the interference of these compounds with hepatic and intrahepatic transport processes on a cellular level.