Combined computational-experimental approach to predict blood–brain barrier (BBB) permeation based on “green” salting-out thin layer chromatography supported by simple molecular descriptors

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The objective of this paper is to build QSRR/QSAR model for predicting the blood–brain barrier (BBB) permeability. The obtained models are based on salting-out thin layer chromatography (SOTLC) constants and calculated molecular descriptors. Among chromatographic methods SOTLC was chosen, since the mobile phases are free of organic solvent. As consequences, there are less toxic, and have lower environmental impact compared to classical reserved phases liquid chromatography (RPLC). During the study three stationary phase silica gel, cellulose plates and neutral aluminum oxide were examined. The model set of solutes presents a wide range of log BB values, containing compounds which cross the BBB readily and molecules poorly distributed to the brain including drugs acting on the nervous system as well as peripheral acting drugs. Additionally, the comparison of three regression models: multiple linear regression (MLR), partial least-squares (PLS) and orthogonal partial least squares (OPLS) were performed. The designed QSRR/QSAR models could be useful to predict BBB of systematically synthesized newly compounds in the drug development pipeline and are attractive alternatives of time-consuming and demanding directed methods for log BB measurement. The study also shown that among several regression techniques, significant differences can be obtained in models performance, measured by R2 and Q2, hence it is strongly suggested to evaluate all available options as MLR, PLS and OPLS.HighlightsApplication of “green” SOTLC in QSAR study.Compression of SOTLC stationary phases (silica gel, aluminum oxide, cellulose) as potential tools supporting log BB prediction.QSRR/QSAR regression models for predicting the blood–brain barrier (BBB) permeability were proposed.

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