Identification of Key Structural Characteristics of Schisandra chinensis Lignans Involved in P-Glycoprotein Inhibition
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- 作者：Ji艡铆 Slanina ; Gabriela P谩chnikov谩 ; Martina 膶arneck谩 ; Ludmila Porubov谩 Koub铆kov谩 ; Lenka Ad谩mkov谩 ; Otakar Humpa ; Karel 艩mejkal ; Iva Slaninov谩
- 刊名：Journal of Natural Products
- 出版年：2014
- 出版时间：October 24, 2014
- 年：2014
- 卷：77
- 期：10
- 页码：2255-2263
- 全文大小：387K
- ISSN：1520-6025
文摘
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鈥揳ctivity 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, (鈭?-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.