Novel flavonolignan hybrid antioxidants: From enzymatic preparation to molecular rationalization
Language English Country France Media print-electronic
Document type Journal Article
PubMed
28068598
DOI
10.1016/j.ejmech.2016.12.051
PII: S0223-5234(16)31057-1
Knihovny.cz E-resources
- Keywords
- Cytoprotection, Enzymatic coupling, Lipid peroxidation, Multipotent antioxidant, Silybin, Vitamin C,
- MeSH
- Antioxidants chemistry metabolism pharmacology MeSH
- Cell Membrane metabolism MeSH
- Hep G2 Cells MeSH
- Cytoprotection drug effects MeSH
- Enzymes, Immobilized MeSH
- Flavonolignans chemistry metabolism pharmacology MeSH
- Fungal Proteins MeSH
- Liver cytology drug effects metabolism MeSH
- Humans MeSH
- Lipase metabolism MeSH
- Molecular Conformation MeSH
- Lipid Peroxidation drug effects MeSH
- Silybin MeSH
- Silymarin chemistry MeSH
- Molecular Dynamics Simulation MeSH
- Electron Transport MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antioxidants MeSH
- Enzymes, Immobilized MeSH
- Flavonolignans MeSH
- Fungal Proteins MeSH
- Lipase MeSH
- Novozyme 435 MeSH Browser
- Silybin MeSH
- Silymarin MeSH
A series of antioxidants was designed and synthesized based on conjugation of the hepatoprotective flavonolignan silybin with l-ascorbic acid, trolox alcohol or tyrosol via a C12 aliphatic linker. These hybrid molecules were prepared from 12-vinyl dodecanedioate-23-O-silybin using the enzymatic regioselective acylation procedure with Novozym 435 (lipase B) or with lipase PS. Voltammetric analyses showed that the silybin-ascorbic acid conjugate exhibited excellent electron donating ability, in comparison to the other conjugates. Free radical scavenging, antioxidant activities and cytoprotective action were evaluated. The silybin-ascorbic acid hybrid exhibited the best activities (IC50 = 30.2 μM) in terms of lipid peroxidation inhibition. The promising protective action of the conjugate against lipid peroxidation can be attributed to modulated electron transfer abilities of both the silybin and ascorbate moieties, but also to the hydrophobic C12 linker facilitating membrane insertion. This was supported experimentally and theoretically by density functional theory (DFT) and molecular dynamics (MD) calculations. The results presented here can be used in the further development of novel multipotent antioxidants and cytoprotective agents, in particular for substances acting at an aqueous/lipid interface.
References provided by Crossref.org
Preparation of Retinoyl-Flavonolignan Hybrids and Their Antioxidant Properties
Sulfated Metabolites of Flavonolignans and 2,3-Dehydroflavonolignans: Preparation and Properties
