Informace o publikaci

Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition

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SLANINA Jiří PÁCHNIKOVÁ Gabriela ČARNECKÁ Martina KOUBÍKOVÁ Ludmila ADÁMKOVÁ Lenka HUMPA Otakar ŠMEJKAL Karel SLANINOVÁ Iva

Rok publikování 2014
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Natural Products
Fakulta / Pracoviště MU

Lékařská fakulta

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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