A new descriptor via bio-mimetic chromatography and modeling for the blood brain barrier (Part II)

Publication date: Available online 25 May 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Maria G. Kouskoura, Aikaterini I. Piteni, Catherine K. MarkopoulouAbstractWithin the context of drug design methodology for the central nervous system (CNS), a predictive model which can shorten the process of finding new candidate drugs was developed. Therefore, the retention time of 51 molecules which are clinically established to enter the blood brain barrier (BBB), were recorded on two HPLC columns. For this purpose, a lipophilic butyl (C4) stationary phase was used to simulate the behavior of a drug regarding BBB permeability and a zwitterionic-HILIC to simulate blood.The results were plotted as Y variables on two Partial Least Squares (PLS) models, while 25 specific physicochemical properties (significant for lipid bilayers BBB permeation or blood) were used as X descriptors. Both models can be utilized to predict the drugability of a new molecule avoiding needless animal experiments, as well as time and material consuming syntheses. The developed models were validated (R2 ≥ 0.90, Q2 ≥ 0.83), and based on the results specific variables were proved to be significant for the studied phenomenon.Additionally, a new factor symbolized as MT was introduced. MT incorporated the experimental results and it was calculated by the fraction of the sum of the retention time of the drug on the two columns (tr(butyl) + tr(HILIC)) divided by the molecular vol...

Source: Journal of Pharmaceutical and Biomedical Analysis - July 10, 2018 Category: Drugs & Pharmacology Source Type: research