Identification of key structural characteristics of Schisandra chinensis lignans involved in P-glycoprotein inhibition
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25302569
DOI
10.1021/np500521v
Knihovny.cz E-resources
- MeSH
- Cyclooctanes * chemistry isolation & purification pharmacology MeSH
- Doxorubicin pharmacology MeSH
- G2 Phase Cell Cycle Checkpoints drug effects MeSH
- Quantitative Structure-Activity Relationship MeSH
- Humans MeSH
- Lignans * chemistry isolation & purification pharmacology MeSH
- Molecular Structure MeSH
- ATP Binding Cassette Transporter, Subfamily B antagonists & inhibitors MeSH
- Polycyclic Compounds * chemistry isolation & purification pharmacology MeSH
- Schisandra chemistry MeSH
- Seeds chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Russia MeSH
- Names of Substances
- Cyclooctanes * MeSH
- dibenzocyclooctadiene lignan MeSH Browser
- Doxorubicin MeSH
- Lignans * MeSH
- ATP Binding Cassette Transporter, Subfamily B MeSH
- Polycyclic Compounds * MeSH
- schizandrin A MeSH Browser
- schizandrin B MeSH Browser
The aim of the present study was to determine the structural requirements for dibenzocyclooctadiene lignans essential for P-glycoprotein inhibition. Altogether 15 structurally related lignans isolated from Schisandra chinensis or prepared by modification of their backbone were investigated, including three pairs of enantiomers. P-Glycoprotein inhibition was quantified using a doxorubicin accumulation assay in human promyelotic leukemia HL60/MDR cells overexpressing P-glycoprotein. A preliminary quantitative structure-activity relationship analysis revealed three main structural features involved in P-glycoprotein inhibition: a 1,2,3-trimethoxy moiety, a 6-acyloxy group, and the absence of a 7-hydroxy group. The most effective inhibitors, (-)-gomisin N (1) and (+)-deoxyschizandrin [(+)-2], were selected for further evaluation of their effects. Both these lignans restored the cytotoxic effect of doxorubicin in HL60/MDR cells and when combined with a subtoxic concentration of this compound increased the proportion of G2/M cells significantly, which is a usual response to treatment with this anticancer drug.
References provided by Crossref.org
Quaternary Benzophenanthridine Alkaloids Act as Smac Mimetics and Overcome Resistance to Apoptosis
Screening of Natural Compounds as P-Glycoprotein Inhibitors against Multidrug Resistance
