Cytotoxic effect of carbohydrate derivatives of digitoxigenin involves modulation of plasma membrane Ca -ATPase.

Cardiac glycosides, such as digoxin and digitoxin, are compounds that interact with Na /K -ATPase to induce anti-neoplastic effects; however, these cardiac glycosides have narrow therapeutic index. Thus, semi-synthetic analogs of digitoxin with modifications in the sugar moiety has been shown to be an interesting approach to obtain more selective and more effective analogs than the parent natural product. Therefore, the aim of this study was to assess the cytotoxic potential of novel digitoxigenin derivatives, digitoxigenin-α-L-rhamno-pyranoside (1) and digitoxigenin-α-L-amiceto-pyranoside (2), in cervical carcinoma cells (HeLa) and human diploid lung fibroblasts (Wi-26-VA4).

Conformational states of the pig kidney Na/K-ATPase differently affect bufadienolides and cardenolides: A directed structure-activity and structure-kinetics study.

There is a renewed interest in the Na/K-ATPase (NKA, EC 3.6.3.

Revisiting the binding kinetics and inhibitory potency of cardiac glycosides on Na,K-ATPase (α1β1): Methodological considerations.

Introduction: Ouabain and digoxin are classical inhibitors of the Na,K-ATPase. In addition to their conventional uses as therapeutic agents or experimental tools there is renewed interest due to evidence suggesting they could be endogenous hormones. Somewhat surprisingly, different publications show large discrepancies in potency for inhibiting Na,K-ATPase activity (IC), particularly for the slow binding inhibitors, ouabain and digoxin.