Identification of key structural characteristics of Schisandra chinensis lignans involved in P-glycoprotein inhibition
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25302569
DOI
10.1021/np500521v
Knihovny.cz E-zdroje
- MeSH
- cyklooktany * chemie izolace a purifikace farmakologie MeSH
- doxorubicin farmakologie MeSH
- kontrolní body fáze G2 buněčného cyklu účinky léků MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- lidé MeSH
- lignany * chemie izolace a purifikace farmakologie MeSH
- molekulární struktura MeSH
- P-glykoproteiny antagonisté a inhibitory MeSH
- polycyklické sloučeniny * chemie izolace a purifikace farmakologie MeSH
- Schisandra chemie MeSH
- semena rostlinná chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Rusko MeSH
- Názvy látek
- cyklooktany * MeSH
- dibenzocyclooctadiene lignan MeSH Prohlížeč
- doxorubicin MeSH
- lignany * MeSH
- P-glykoproteiny MeSH
- polycyklické sloučeniny * MeSH
- schizandrin A MeSH Prohlížeč
- schizandrin B MeSH Prohlížeč
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.
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