Retention data of bile acids and their oxo derivatives in characterization of pharmacokinetic properties and in silico ADME modeling.

摘要: Abstract Purpose Information on ADME properties of examined bile acids and their oxo derivatives are scarce, although the interest for use in nanochemistry macromolecular chemistry is increasing. The purpose this research was to evaluate lipophilicity, a crucial physicochemical parameter describing selected derivatives, compare two approaches: experimentally determined hydrophobicity parameters calculated log P values. Methods Commercially available - deoxycholic, chenodeoxycholic, hyodeoxycholic ursodeoxycholic acid were used synthesize derivatives. Lipophilicity evaluated solvent systems: toluene/ethanol toluene/butanol. Retention acquired by normal-phase TLC. correlations between values obtained using five different software ( R M 0 (tol/eth) , (tol/but) b ) examined. Results Correlation analysis confirmed significant dependence experimental parameters. suggest satisfactory intestinal absorption after oral administration all compounds as well low volumes distribution, high affinity binding with plasma proteins. Penetration through blood-brain barrier skin not satisfactory. All show G-protein coupled receptors consequently inhibition ionic channels. also possible nuclear receptors. Conclusions Established lipophilicity testing model studied showed excellent predictive ability might represent tool development relations chromatographic behavior properties. Compounds 3α-hydroxy-7,12-dioxo-5β-cholanoic 12α-hydroxy-3,7-dioxo-5β-cholanoic be most suitable candidates further studies (satisfactory pharmacokinetic lowest haemolytic potential) followed 3α-hydroxy-12-oxo-5β-cholanoic 3α-hydroxy-7-oxo-5β-cholanoic (slightly higher potential, but better ligand properties).