Prediction of Lipophilicity and Pharmacokinetics of Chloroacetamides by Chemometric Approach

Document Type: Research article

Authors

Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.

Abstract

In this study, the existence of biological potential of selected N-(substituted phenyl)-2-
chloroacetamides was examined none empirically, as was the possibility of applying simple
experimental technique in predicting essential properties which affect the biological activity
of the compounds. By applying the Lipinski and Ghose’s rules, it has been revealed that the
examined chloroacetamides fulfill the theoretical requirements for bioactive compounds.
In addition, lipophilicity was determined by applying the reversed-phase thin-layer
chromatography (RPTLC18F254s) in the mixtures of water and two organic modifiers separately
(methanol and acetone) and by using relevant software packages. The chromatographic
retention parameters, RM
0 and m, as the presumed criteria for the lipophilicity of the examined
chloroacetamides were correlated by linear regression analysis, and the relevant chemometric
methods (Cluster Analysis and Principal Component Analysis) with the standard measure of
lipophilicity, log P, and with the selected pharmacokinetic predictors. Thus good correlations
in both water-modifier systems (average correlation coefficients, r , 0.947 and 0.931) were
obtained. The chemometric methods, as well as the classical correlation methods gave similar
results which demonstrated that the chromatographic retention parameters, RM
0 and m, can
successfully describe the lipophilicity and the pharmacokinetics of the N-(substituted phenyl)-
2-chloroacetamides in the first steps of preclinical research.

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