The relative role of polar and nonpolar factors of the structure of substance on the process of their penetration through the blood–brain barrier

Abstract

The analysis of the relative role of polar and non-polar factors of the molecular structure on the penetration of substances through the blood–brain barrier (BBB) was carried out. Such analysis will allow a preliminary approximate assessment of the ability of substances to cross the blood–brain barrier. Using previously developed computer expert systems on the basis of QSAR/QSPR models in the framework of simplex approach, the water solubility logSw (polar factor model), the lipophilicity logP (nonpolar factor model), and the characteristics of penetration through the blood–brain barrier (logBB, logPS, logP0PAMPA–BBB) were calculated for a set of 614 different organic compounds. It was determined whether substances belong to classes BBB+ or BBB– and whether these substances are substrates of P-glycoprotein (P-gl) or not (no-P-gl). Analysis of the distribution of the points of the investigated molecules in the logP vs. logSw coordinates revealed that lipophilicity and water solubility for the compounds with high penetrating ability should be approximately in following ranges: 3logP6; and –5logSw–1. For the data, which are presented in different scales, continuous scale and classification scale, a half-sign correlation coefficient Rss was calculated. Rss equals 0.93, that confirms the consistency of the results of the prognosis of Log BB parameters and classification BBB+/BBB–. The general trends in the classification of the investigated compounds according to the BBB+/BBB– and P-gl/no-P-gl classes were quantitatively estimated. The sign coefficient of association, which equals –0.35, emphasizes the antibatic nature of the relationship between the data of the two classifications.