Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition
| Autoři | |
|---|---|
| Rok publikování | 2014 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Journal of Natural Products |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.1021/np500521v |
| Obor | Farmakologie a lékárnická chemie |
| Klíčová slova | RESISTANCE-ASSOCIATED PROTEIN-1; MEDIATED MULTIDRUG-RESISTANCE; CANCER-CELLS; DIBENZOCYCLOOCTADIENE LIGNANS; ABSOLUTE STRUCTURE; DRUG-RESISTANCE; GOMISIN-N; CONSTITUENTS; BAILL; SCHIZANDRIN |
| Přiložené soubory | |
| Popis | 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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