Quantitative structure-activity relationships of cardiotonic steroids using empirical molecular electrostatic potentials and semiempirical molecular orbital calculations

Abstract

Empirical molecular electrostatic potentials and a rigid receptor H atom model are used to calculate differences in the interaction energy of cardiotonic steroids with the digitalis receptor. An attempt is made to map the receptor H binding sites for two different steroid conformations with respect to 17β side-chain orientation. The calculated interaction energies using single-crystal X-ray structure data indicate linear relationships with the Na +, K +-ATPase inhibitory activity. On the basis of these correlations, the activity of 8 so far pharmacologically not investigated steroids containing CO in 17β substituents are estimated with the help of structural data determined by means of the semiempirical CNDO molecular orbital theory.