Combined Micellar Liquid Chromatography Technique and QSARs Modeling in Predicting the Blood–Brain Barrier Permeation of Heterocyclic Drug-like Compounds

Abstract

The quantitative structure–activity relationship (QSAR) methodology was used to predict the blood–brain permeability (log BB) for 65 synthetic heterocyclic compounds tested as promising drug candidates. The compounds were characterized by different descriptors: lipophilicity, parachor, polarizability, molecular weight, number of hydrogen bond acceptors, number of rotatable bonds, and polar surface area. Lipophilic properties of the compounds were evaluated experimentally by micellar liquid chromatography (MLC). In the experiments, sodium dodecyl sulfate (SDS) as the effluent component and the ODS-2 column were used. Using multiple linear regression and leave-one-out cross-validation, we derived the statistically significant and highly predictive quantitative structure–activity relationship models. Thus, this study provides valuable information on the expected properties of the substances that can be used as a support tool in the design of new therapeutic agents.

Keywords

• micellar chromatography
• QSARs
• log <i>BB</i>
• lipophilicity
• heterocyclic drug-like compounds