Combined Micellar Liquid Chromatography Technique and QSARs Modeling in Predicting the Blood-Brain Barrier Permeation of Heterocyclic Drug-like Compounds.
Małgorzata JanickaAnna MyckaMałgorzata SztankeKrzysztof SztankePublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- structure activity relationship
- liquid chromatography
- mass spectrometry
- high resolution mass spectrometry
- tandem mass spectrometry
- simultaneous determination
- white matter
- drinking water
- molecular dynamics
- healthcare
- multiple sclerosis
- solid phase extraction
- emergency department
- wastewater treatment
- adverse drug
- endothelial cells
- resting state
- blood brain barrier
- brain injury
- functional connectivity
- ionic liquid
- recombinant human