Inhibition of Na+,K+-ATPase by flavonoids and their positive inotropic effect.: Investigation of the structure-activity relationship

The relationship between the structures of 39 natural flavonoids, including flavones, flavonols, flavanones, and isoflavones, and their inhibitory and positive inotropic effects Has been found. It has shown that certain (but not all) flavonoids considerably inhibit the activity of the purified preparation of pig kidney medulla Na+, K+-ATPase with K-i = 1.4-22.2 mu M and exert positive inotropic effect on the papillary muscle. Flavones and flavonols, containing hydroxyl groups in side phenyl radical in ortho-or vicinal positions exhibit high inhibitory and positive inotropic effects. The inhibitory and positive ionotropic effects of flavonoid glycosides and methoxyflavonoids are less pronounced. The presence of dymethylallyl groups in flavonones lead to the increace in the inhibitory and positive inotropic activities. Isoflavones produced virtually no effect on the enzyme and the isolated heart muscle. The effect of quercetin on the structure Na+, K+-ATPase was studied by the fluorescence method.