| Abstract: | Hellebrigenin, which diflers from strophanthidin only in its lactone ring, has 30 times the affinity of strophanthidin for the brain (Na + K)-activated adenosinetriphosphatase. Hellebrigenin 3-acetate and hellebrigenin 3,5-diacetate are about three times more potent toward this enzyme than hellebrigenin is. The 3-iodoacetate and 3-bromoacetate of hellebrigenin were synthesized and were highly potent irreversible inhibitors of the enzyme. The iodoacetate was 20 times more potent than the bromoacetate, as expected from the superior alkylating power of iodoacetate as compared to bromoacetate. The irreversible inhibition of the enzyme by hellebrigenin 3-bromoacetate and by strophanthidin 3-bromoacetate paralleled the affinities of the nonesterified steroids for reversible inhibition; this is further strong evidence for the site-directed alkylation of the (Na + K)-activated sinetriphosphatase by the haloacetate derivatives of the cardiotonic steroids. |
