Identification of key structural characteristics of Schisandra chinensis lignans involved in P-glycoprotein inhibition.
Basic Information
ID: ALA3351498
Journal: J Nat Prod
Title: Identification of key structural characteristics of Schisandra chinensis lignans involved in P-glycoprotein inhibition.
Authors: Slanina J, Páchniková G, Carnecká M, Porubová Koubíková L, Adámková L, Humpa O, Smejkal K, Slaninová I.
Abstract: 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.
CiteXplore: 25302569
DOI: 10.1021/np500521v
Patent ID: ┄