Effects of synthetic and naturally occurring flavonoids on Na sup + , K sup + -ATPase: Aspects of the structure-activity relationship and action mechanism
- Tokyo College of Pharmacy (Japan)
A comparative study was made of the effects of 15 synthetic and naturally occurring flavonoids on the hydrolytic activity of Na{sup +}, K{sup +} -adenosine triphosphatase (ATPase). Twelve of the flavonoids examined were mono-hydroxy or mono-methoxy derivatives. All inhibited Na{sup +}, K{sup +} -ATPase from dog kidney cortex when present at concentrations from 40-1000 {mu}M. Flavones possessing cyclohexyl instead of the phenyl group were the most potent with IC{sub 50} at 257-320 {mu}M. Structure-activity relationships were observed among the following mono-substituted flavones as: (i) 2-cyclohexyl-benzopyran-4-one {much gt} 2-phenyl-benzopyran-4-one; (ii) 2-cyclohexyl-7-hydroxybenzopyran-4-one {gt} 2-cyclohexyl-6-hydroxy-benzopyran-4-one {gt} 2-cyclohexyl-5-hydroxybenzopyran-4-one. Some flavonoids showing potent inhibitory activity were also examined for ouabain-displacement activity on human erythrocytes. Hardly and of the flavonoids were able to block ({sup 3}H) ouabain binding to erythrocytes. These results suggest that the mechanism by which flavonoid block Na{sup +}, K{sup +} -ATPase is not related to the cardiac glycoside-specific binding site(s) of this enzyme.
- OSTI ID:
- 5102099
- Journal Information:
- Life Sciences; (USA), Vol. 45:12; ISSN 0024-3205
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ATP-ASE
ENZYME ACTIVITY
FLAVENOIDS
BIOCHEMICAL REACTION KINETICS
COMPARATIVE EVALUATIONS
DOGS
ERYTHROCYTES
INHIBITION
KIDNEYS
MAN
OUABAIN
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ACID ANHYDRASES
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
DRUGS
ENZYMES
GLYCOSIDES
HYDROGEN COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PHOSPHOHYDROLASES
PRIMATES
PROTEINS
REACTION KINETICS
STROPHANTHINS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques