Synthesis of dibenzocyclooctadiene lignans derivatives as P-glycoprotein inhibitors
| Title in English | 53rd Advances in Organic, Bioorganic and Pharmaceutical Chemistry "Liblice 2018" |
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| Authors | |
| Year of publication | 2018 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | In previous work, the structural requirements for P-glycoprotein inhibition by dibenzocyclooctadiene lignans were studied. P-Glycoprotein inhibition was quantified using flow cytometry doxorubicin accumulation assay in resistant human acute promyelocytic leukaemia cells overexpressing P-glycoprotein (HL60/MDR). 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 lignans restored the cytotoxic effect of doxorubicin in HL60/MDR cells. The five most effective dibenzocyclooctadiene lignans have met two of the three conditions; however, none of the 14 lignans tested fulfilled all three structural prerequisites.1 Our current work is directed towards a greater number of suitable lignans to gain a deeper insight into the structure-to-activity relationship and to obtain more effective inhibitors. The lignans isolated from Schisandra chinensis extracts are modified to increase the effectiveness of P-glycoprotein inhibition. The 7-hydroxy group, which decreases the activity of lignans, was modified by acetylation, dehydration and methylation. The acetylated derivatives of schizandrin and gomisin A were prepared. |
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