Prenylated xanthones as potential P-glycoprotein modulators.
Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1) were prepared. Their activity as potential P-glycoprotein inhibitors was monitored by affinity of direct binding and compared to that of corresponding DMA-flavones. Both classes of compounds exhibited the same structure-activity relationships. Decreasing polarity enhanced the binding affinity for the P-glycoprotein C-terminal cytosolic domain since DMA derivatives were more active, but unsubstituted hydroxyl group close to the carbonyl was required for efficient activity.
Tchamo
D N
DN
Laboratoire de Pharmacognosie, DPM (UMR 5063 CNRS-UJF), Université Grenoble I, Faculté de Pharmacie, La Tronche, France.
Dijoux-Franca
M G
MG
Mariotte
A M
AM
Tsamo
E
E
Daskiewicz
J B
JB
Bayet
C
C
Barron
D
D
Conseil
G
G
Di Pietro
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000737:chemistry / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014970:Xanthines