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 squar...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2014-04, Vol.19 (4), p.4115-4134
Main Authors: Vavříková, Eva, Vacek, Jan, Valentová, Kateřina, Marhol, Petr, Ulrichová, Jitka, Kuzma, Marek, Křen, Vladimír
Format: Article
Language:English
Subjects:
Adults
Alzheimer's disease
Animals
antioxidant
Antioxidants
Biocatalysis
Biological
Biological activity
Biphenyl Compounds - antagonists & inhibitors
Cell Survival - drug effects
Cytotoxicity
Dimerization
Dimers
electrochemistry
Electrodes
Fibroblasts - cytology
Fibroblasts - drug effects
Flavonoids
flavonolignan
Free Radical Scavengers - chemical synthesis
Free Radical Scavengers - pharmacology
Fungal Proteins - chemistry
Hep G2 Cells
Human
Human Umbilical Vein Endothelial Cells
Humans
HUVEC
Keratinocytes - cytology
Keratinocytes - drug effects
Lipase - chemistry
Lipid Peroxidation - drug effects
Mice
microsomal lipid peroxidation
Microsomes, Liver - drug effects
Monomers
Oxidation
Oxidation-Reduction
Picrates - antagonists & inhibitors
Rats
silibinin
Silybin
Silymarin - chemical synthesis
Silymarin - pharmacology
Surface chemistry
Veins
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Summary: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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules19044115