Prediction of In Silico ADME Properties of 1,2-O-Isopropylidene Aldohexose Derivatives

Abstract

Retention behavior of molecules mostly depends on their chemical structure. Retention data of biologically active molecules could be an indirect relationship between their structure and biological or pharmacological activity, since the molecular structure affects their behavior in all pharmacokinetic stages. In the present paper, retention parameters (RM0) of biologically active 1,2-O-isopropylidene aldohexose derivatives, obtained by normal-phase thin-layer chromatography (NP TLC), were correlated with selected physicochemical properties relevant to pharmacokinetics, i.e. absorption, distribution, metabolism, and elimination (ADME) properties. Conducted correlation analysis showed high dependence between RM0 and blood brain barrier penetration, skin permeability, enzyme inhibition, bonding affinity to nuclear receptor ligand and G protein-coupled receptors, as well as lipophilicity (expressed as Hansh-Leo's parameter Clog P). The statistical validity of the established polynomial dependence of the second degree between RM0 and mentioned ADME properties was confirmed by standard statistical measures and leave-one-out cross-validation method. On the basis of in silico calculated ADME properties and retention data, the similarity between studied molecules was examined using principal component analysis (PCA). The obtained results indicate the possibility of predicting ADME properties of studied compounds on the basis of their retention data (RM0). These preliminary results could be treated as guideline for selecting new 1,2-O-isopropylidene aldohexose derivatives as drug candidates.