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-dt-3, 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) corresponded to affinity measurements in all but two cases: dehydro-dt-3 and dehydro-dt-2 showed very low I50 values. © 1979 Springer-Verlag.