Heuman indices of hydrophobicity of bile acids and their comparison with a newly developed and conventional molecular descriptors

Abstract

Bile salts (BSs), in addition to their physiological role in the digestion of lipids in vertebrates, are also of significant importance in biomedical investigations. For predicting biological-pharmacological activity and physico-chemical properties of BSs it is important to develop such molecular descriptors that adequately describe the structural characteristics of the steroid skeleton. The present study encompassed the following bile acids (BAs): cholic, chenodeoxycholic, deoxycholic, hyodeoxycholic, ursodeoxycholic, hyocholic, and ursocholic acid, as well as oxo derivatives of certain BAs. For all of them, Heuman hydrophobicity indices (HIBA) (RP-HPLC parameters) were determined, and a detailed conformational analysis of the steroid skeleton showed that HIBA has the discrimination power for BAs based on the size of the hydrophobic surface on the β side and the lateral L7 and L12 sides of the steroid skeleton. Also, HIBA discerns the regiochemical characteristics of OH and oxo groups. Based on a survey of the structural factors of the steroid skeleton that influence the HI BA values of the tested BAs, we constructed a new molecular descriptor, CHIBA, with the characteristics of 2D and 3D topological descriptors. In respect of the structure of the steroid skeleton, the descriptor CHIBA behaves as a reversed-phase chromatographic descriptor of BAs. © 2013 Elsevier Masson SAS. All rights reserved.