Inhibition of Na+,K+-ATPase by the cardenolide 6'-O-(E-4-hydroxycinnamoyl) desglucouzarin.
Among the major cardenolides from the milkweed Asclepias asperula, 6'-O-(E-4-hydroxycinnamoyl) desglucouzarin has not been characterized biochemically. In this study, its binding affinity for a physiological receptor, porcine kidney Na+,K+-ATPase, was found to be lower than the other cardenolides in this plant. The order of affinities from highest to lowest was: uzarigenin (Kd = 1.05 microM) = desglucouzarin (Kd = 0.98 microM) > uzarin (Kd = 4.0 microM) > 6'-O-(E-4-hydroxycinnamoyl) desglucouzarin (Kd = 16 microM). The chemical attachment of the 4-hydroxycinnamoyl group to the 6'-carbon of desglucouzarin significantly inhibits binding. This agrees with predictions that a 5'-methyl group on cardenolides fits the receptor site optimally for the porcine kidney enzyme. The 4-hydroxycinnamic ester was also found to be fluorescent.
Abbott
A J
AJ
Department of Chemistry & Physics, Louisiana State University at Shreveport, Shreveport, Louisiana, 71115, USA.
Holoubek
C G
CG
Martin
R A
RA
D002298:Cardenolides / Q000737:chemistry / Q000494:pharmacology*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013050:Spectrometry, Fluorescence
C115417:6'-O-(4-hydroxycinnamoyl)desglucouzarin; D002298:Cardenolides; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D000254:Sodium-Potassium-Exchanging ATPase; D003474:Curcumin