New derivatives of silybin and 2,3-dehydrosilybin and their cytotoxic and P-glycoprotein modulatory activity
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16466920
DOI
10.1016/j.bmc.2006.01.035
PII: S0968-0896(06)00060-5
Knihovny.cz E-resources
- MeSH
- Alkylation MeSH
- Drug Resistance, Neoplasm MeSH
- Drug Screening Assays, Antitumor MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy MeSH
- Molecular Structure MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Tumor Cells, Cultured MeSH
- Oxidation-Reduction MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 antagonists & inhibitors MeSH
- Cell Proliferation drug effects MeSH
- Silybin MeSH
- Silymarin chemical synthesis chemistry pharmacology MeSH
- Stereoisomerism MeSH
- Cell Survival drug effects MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
- Silybin MeSH
- Silymarin MeSH
Large series of O-alkyl derivatives (methyl and benzyl) of silybin and 2,3-dehydrosilybin was prepared. Selective alkylation of the silybin molecule was systematically investigated. For the first time we present here, for example, preparation of 19-nor-2,3-dehydrosilybin. All prepared silybin/2,3-dehydrosilybin derivatives were tested for cytotoxicity on a panel of drugs sensitive against multidrug resistant cell lines and the ability to inhibit P-glycoprotein mediated efflux activity. We have identified effective and relatively non-cytotoxic inhibitors of P-gp derived from 2,3-dehydrosilybin. Some of them were more effective inhibitors at concentrations lower than a standard P-gp efflux inhibitor cyclosporin A. Another group of 2,3-dehydrosilybin derivatives also had better inhibitory effects on P-gp efflux but a cytotoxicity comparable with that of parent 2,3-dehydrosilybin. Structural requirements for improving inhibitory activity and reducing toxicity of 2,3-dehydrosilybin were established. Effect of E-ring substitution as well as an influence of the substituent size at the C-7-OH position of A-ring on P-gp-inhibitory activity was evaluated for the first time in this study.
References provided by Crossref.org
Chirality Matters: Biological Activity of Optically Pure Silybin and Its Congeners
Preparation of Retinoyl-Flavonolignan Hybrids and Their Antioxidant Properties
Sulfated Metabolites of Flavonolignans and 2,3-Dehydroflavonolignans: Preparation and Properties
