Dehydro-digitoxosides of digitoxigenin and digoxigenin: binding to beef heart (Na+ + K+)-ATPase in relation to unchanged digitoxosides.

Dehydro-digitoxosides are metabolites of digitalis glycosides. In order to study their possible biological activity their affinity to (Na+ + K+)-activated ATPase was determined and compared with unchanged glycosides. Based on the dissociation constants of glycoside-enzyme-complexes, the affinity of the dehydro-digitoxosides ranged in the same order of magnitude as that of the native glycosides. Comparing mono-, bis-, and tris-digitoxosides of digitoxigenin (dt-1, dt-2, dt-3) and of digoxin (dg-1, dg-2, dg-3) with the corresponding dehydrodigitoxosides (3'-dehydro-dt-1, 9'-dehydro-dt-2, 15'-dehydro-dt3, 3'-dehydro-dg-1 and 9'-dehydro-dg-2, respectively) the dehydro-digitoxosides had lower affinities to the enzyme. The highest dissociation constants (KD) were found for 3'-dehydro-dt-1 and 3'-dehydro-dg-1. The half maximal inhibition of (Na+ + K+)-ATPase activity (I50) coresponded to affinity measurements in all but two cases: dehydro-dt-3 and dehydro-dt-2 showed very low I50 values.