title: Blood-brain barrier permeability mechanisms in view of quantitative structure-activity relationships (QSAR).
abstract: 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 logP and either molecular mass (M) or isolated atomic energy (E(isol)), 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- R(LOO)(2) (Q(2)) 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.
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Bujak
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Wiktoria
authors.initials: W
authors.lastname: Struck-Lewicka
authors.affiliation: Department of Forensic Medicine, Medical University of Gdańsk, ul. Dębowa 23, 80-204 Gdańsk, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Kaliszan
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Kaliszan
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland. Electronic address: markusz@gumed.edu.pl.
authors.forename: Michał J
authors.initials: MJ
authors.lastname: Markuszewski
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D016014:Linear Models; D008958:Models, Molecular; D010539:Permeability; D021281:Quantitative Structure-Activity Relationship; D014116:Toxicology / Q000379:methods
keywords: Blood–brain barrier; LogP; Molecular descriptors; Multiple linear regression (MLR); Quantitative structure–activity relationships (QSAR)