Modeling and prediction (correction) of partition coefficients of bile acids and their derivatives by multivariate regression methods.
Different multiple regression methods including forward stepwise multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS) have been applied to the modeling of partition coefficient (lipophilicity) of bile acids and their derivatives by means of 16 different descriptors obtained by using Alchemy package software and retention index R(Mo) as an experimental estimation of lipophilicity. Retention indices for bile acids and their derivatives were determined by reversed phase high-performance thin layer chromatography on RP-18 W bounded stationary phase with methanol-water in different volume proportions as mobile phase. The results achieved concerning the prediction of Log P are highly significant and consistent with the molecular structure of the compounds investigated. The sum of absolute values of the charges on each atom of the molecule, in electrons (SQ), the sum of absolute values of the charges on the nitrogens and oxygens in the molecule, in electrons (SQ(NO)), specific polarizability of a molecule (SP), the third-order connectivity index ((3)chi) and molecular lipophilicity, seem to be dominant in the partition mechanism. In addition, regression models developed have allowed a correct estimation of the partition coefficients of cholic acid (Log P(HA)=2.93; Log P(A)(-)=2.02) as compared with reported experimental values (Log P(HA)=2.02; Log P(A)(-)=1.1).
Sârbu
Costel
C
Babeş-Bolyai University, Faculty of Chemistry and Chemical Engineering, Arany Janos 11, 400028 Cluj-Napoca, Romania. costelsrb@yahoo.co.uk
Onişor
Cristina
C
Posa
Mihalj
M
Kevresan
Slavko
S
Kuhajda
Ksenija
K
D001647:Bile Acids and Salts / Q000737:chemistry*; D019826:Cholic Acid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D008954:Models, Biological; D015999:Multivariate Analysis; D013329:Structure-Activity Relationship
D001647:Bile Acids and Salts; D019826:Cholic Acid