Blood–brain barrier permeability mechanisms in view of quantitative structure–activity relationships (QSAR)

•The prediction of BBB permeability using QSAR models and MLR calculations.•Isolated atomic energy as a new supportive molecular energy-related descriptor in predicting blood–brain distribution.•The obtained QSAR models were validated using both internal and external validation approaches.•First application of the developed QSAR model of BBB permeability to case from the legal medicine.

The goal of the present paper was to develop a quantitative structure–activity relationship (QSAR) method using a simple statistical approach, such as multiple linear regression (MLR) for predicting the blood–brain barrier (BBB) permeability of chemical compounds. The “best” MLR models, comprised log P and either molecular mass (M) or isolated atomic energy (Eisol), tested on a structurally diverse set of 66 compounds, is characterized the by correlation coefficients (R  ) around 0.8. The obtained models were validated using leave-one-out (LOO) cross-validation technique and the correlation coefficient of leave-one-out- RLOO2 (Q2) was at least 0.6. Analysis of a case from legal medicine demonstrated informative value of our QSAR model. To best authors’ knowledge the present study is a first application of the developed QSAR models of BBB permeability to case from the legal medicine. Our data indicate that molecular energy-related descriptors, in combination with the well-known descriptors of lipophilicity may have a supportive value in predicting blood–brain distribution, which is of utmost importance in drug development and toxicological studies.

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