| Autor: |
Slanina, Jiří, Páchniková, Gabriela, Čarnecká, Martina, Porubová Koubíková, Ludmila, Adámková, Lenka, Humpa, Otakar, Šmejkal, Karel, Slaninová, Iva |
| Zdroj: |
Journal of Natural Products; October 2014, Vol. 77 Issue: 10 p2255-2263, 9p |
| Abstrakt: |
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 chinensisor 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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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