Quantitative structure-activity relationships of cardiotonic steroids using empirical molecular electrostatic potentials and semiempirical molecular orbital calculations.
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 17 beta 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 17 beta substituents are estimated with the help of structural data determined by means of the semiempirical CNDO molecular orbital theory.
D002301:Cardiac Glycosides; D002316:Cardiotonic Agents; D004071:Digitalis Glycosides; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D002301:Cardiac Glycosides; D002316:Cardiotonic Agents; D004071:Digitalis Glycosides