Cholesterol solubilization by oxo derivatives of selected bile acids and their membranotoxicity

Abstract

This study is concerned with the effect of the structure of bile acids on the solubilization of cholesterol (cholesterol solubilizing capacity (C Chm) and the equilibrium micellary solubilization of cholesterol (xChm)). It was found that the replacement of the hydroxy group in the bile acid molecule with an oxo group results in a decrease of the solubilization power of cholesterol. The examined bile acids form two linear groups at the plane of critical micellar concentration (CMC) and solubilization power of cholesterol (CChm or xChm). The group I is formed by bile acids with lower CMCs and higher cholesterol solubilites (deoxycholic (1), chenodeoxycholic (2), hyodeoxycholic (3), cholic (8), 12-oxolithocholic (4), and 7-oxolithocholic (5) acids). On the other hand, the group II is formed by bile acids with higher CMCs and lower cholesterol solubilites (7-oxodeoxycholic (9), 12-oxochenodeoxycholic (10), 12α-hydroxy-3,7- dioxocholanic (11), 7,12-dioxolithocholic (12), 3,7-dioxocholanic (6), and 3,12-dioxocholanic (7) acids). The common conformational characteristics of the bile acid molecules was determined (orientation of OH or oxo grups considered to the mean plane of the steroid skeleton). They form joint groups in the plane of CMC - (CChm or xChm), and the linear function (C Chm or xChm) = f(CMC). The osmotic resistance of erythrocytes determines the membranotoxicity of bile acids. 12-Oxolithocholic acid represents the best compromise with regard to the solubilization of cholesterol and membranotoxicity. © 2010 Institute of Organic Chemistry and Biochemistry.