The lead structure in cardiac glycosides is 5 ?,14 ?-androstane-3 ?,14-diol

Abstract

The purpose of the present study was to determine the lead structure in cardiac glycosides at the receptor level, i.e. the minimal structural requirement for specific and powerful receptor recognition. Accordingly 73 digitalis-like acting steroids were characterized as to the concentration effecting half-maximum inhibition of Na,K-ATPase from human cardiac muscle under standardized turnover conditions. Since the K_i value equaled the apparent K_D value, K′_D was expressed in terms of the apparent standard Gibbs energy change ΔG^o′ of steroid interaction with Na,K-ATPase. This allowed the use of the extrathermodynamic approach as a rational way of correlating in a quantitative manner, the potency and structure of the various steroidal compounds.