Chemo-enzymatic synthesis of silybin and 2,3-dehydrosilybin dimers.
Divalent or multivalent molecules often show enhanced biological activity relative to the simple monomeric units. Here we present enzymatically and chemically prepared dimers of the flavonolignans silybin and 2,3-dehydrosilybin. Their electrochemical behavior was studied by in situ and ex situ square wave voltammetry. The oxidation of monomers and dimers was similar, but adsorption onto the electrode and cell surfaces was different. A 1,1-diphenyl-2-picrylhydrazyl (DPPH) and an inhibition of microsomal lipoperoxidation assay were performed with same trend of results for silybin and 2,3-dehydrosilybin dimers. Silybin dimer showed better activity than the monomer, while on the contrary 2,3-dehydrosilybin dimer presented weaker antioxidant/antilipoperoxidant activity than its monomer. Cytotoxicity was evaluated on human umbilical vein endothelial cells, normal human adult keratinocytes, mouse fibroblasts (BALB/c 3T3) and human liver hepatocellular carcinoma cell line (HepG2). Silybin dimer was more cytotoxic than the parent compound and in the case of 2,3-dehydrosilybin its dimer showed weaker cytotoxicity than the monomer.
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic. vavrikova@biomed.cas.cz.
Eva
E
Vavříková
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, CZ-775 15 Olomouc, Czech Republic. jan.vacek@upol.cz.
Jan
J
Vacek
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic. kata.valentova@email.cz.
Kateřina
K
Valentová
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic. rtepm@seznam.cz.
Petr
P
Marhol
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, CZ-775 15 Olomouc, Czech Republic. jitka.ulrichova@upol.cz.
Jitka
J
Ulrichová
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic. kuzma@biomed.cas.cz.
Marek
M
Kuzma
Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-142 20 Prague 4, Czech Republic. kren@biomed.cas.cz.
Vladimír
V
Křen
D000818:Animals; D055162:Biocatalysis; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors; D002470:Cell Survival / Q000187:drug effects; D019281:Dimerization; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000494:pharmacology; D005656:Fungal Proteins / Q000737:chemistry; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008049:Lipase / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects; D010084:Oxidation-Reduction; D010851:Picrates / Q000037:antagonists & inhibitors; D051381:Rats; D000077385:Silybin; D012838:Silymarin / Q000138:chemical synthesis* / Q000494:pharmacology
D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005656:Fungal Proteins; D010851:Picrates; D012838:Silymarin; C515097:dehydrosilybin; D000077385:Silybin; C004931:1,1-diphenyl-2-picrylhydrazyl; D008049:Lipase