[Theoretical study of a structure-activity relationship of cardiotonic steroids]

The calculations have been performed to determine conformations and assess electronic structure of 44 compounds with known cardiotonic activity. Atoms O(3), C(13) and C(18) of all conformations were superimposed on the same atoms of digitoxigenin, and the relationship between the spatial disposition of the side chain carbonyl oxygen and biological activity of the respective compounds was examined. The most active cardiotonics are shown to share very similar topography. B- or A-conformations are active for cardenolides or bufadienolides, respectively. Some correlations between the structure and cardiotonic activity were disclosed. The principles for cardiotonic drug design are formulated and some formulas of new potentially active compounds are suggested.