Abstract

We have previously suggested that an inhibitor of the sodium pump derived from human placentas might be a bufenolide (dihydropyrone-substituted steroid) but the mass-spectral analysis that led to this conclusion gave no information as to stereochemistry. We have therefore attempted to synthesise a wide range of bufadienolides and bufenolides as model compounds using the Suzuki approach to coupling α-pyrone to androsterone. We report here the effect of 3β-OH, 5β,14β bufadienolide on four sodium pumps in vitro, human leucocytes, human erythrocytes, dog kidney ATP-ase and pig brain ATP-ase.

When exposed to increasing concentrations of the compound there was a smaller reduction in the activity of the sodium pump of human erythrocytes as compared with the dog and pig ATP-ases. This difference was more marked in the case of human leucocytes where 50% inhibition was not achieved and this suggests that the compound may be inhibiting subsets of the sodium pump to different degrees. The concentration range in which this compound is active makes it an unlikely candidate for an endogenous regulator but its differential activity on the ATP-ases suggests that it may share some important characteristics with the natural compound. It is uncertain whether the differences in activity observed here correspond to the known isoforms of the sodium pump. (See Figure)