Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect

PIWIEN-PILIPUK G, KANELAKIS KC, GALIGNIANA MD

EUROPEAN JOURNAL OF PHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2002 vol. 454 p. 131 - 143

0014-2999

The aim of this study was to correlate mineralocorticoid action and steroid structure. Inasmuch as Na(+) retention follows a parabolic dose-response curve for most pregnanesteroids, the second-order coefficient of the function was used as a representative factor for this bipartite biological effect. The C(3)=O/D angle of the ligands was correlated with both Na(+)-retaining activity and binding affinity for the mineralocorticoid receptor. Because some steroids exhibit identical functional groups and different conformational structure, we also postulate that the flat conformation of a pregnanesteroid determines its Na(+)-retaining capacity in vivo. No correlations were found in vitro, which demonstrates the multifactorial nature of the second-order coefficient determined in vivo under more complex and interactive conditions that include various pre-receptor variables. These findings may allow the estimation of the putative biological activity of a given steroid simply by knowing its conformational structure, which may be important for designing compounds in a pharmaceutical setting.