Prediction of the Blood-Brain Barrier Permeability Using RP-18 Thin Layer Chromatography

Published on Feb 2, 2019in Central European Journal of Chemistry
· DOI :10.1515/CHEM-2019-0005
Anna W. Sobańska10
Estimated H-index: 10
(Medical University of Łódź),
Karolina Wanat3
Estimated H-index: 3
(Medical University of Łódź),
Elżbieta Brzezińska9
Estimated H-index: 9
(Medical University of Łódź)
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Abstract
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A review of applications of thin layer chromatography (TLC) in drug discovery is given. TLC is presented as a tool to determine the solutes physicochemical properties (lipophilicity, dissociation constant, water solubility) and to predict the interactions of drugs with biomembranes, blood-brain barrier permeability, plasma protein binding, volume of distribution, gastric and skin absorption. Results of modeling based on thin layer chromatographic descriptors are correlated with those obtained by...
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Abstract The review is mainly focused on application of thin layer chromatography (TLC) as simple, rapid and inexpensive method for lipophilicity assessment. Among separation techniques, TLC is still one of the most popular for lipophilicity measurement. The principles and methodology of Quantitative Structure Retention Relationship (QSRR) employed to lipophilicity prediction from retention data are presented. Moreover, applications of TLC retention constants in Quantitative Structure Activity R...
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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 stu...
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Chemical ultraviolet (UV) filters and preservatives used currently in sunscreen preparations are compounds of diverse structures, and the safety of their application depends on their inability to penetrate the skin and other barriers present in the human body. However, at least some of these chemicals meet the general requirements of the good blood—brain barrier (BBB) permeability described in the literature sources. The objective of this study was to examine the behavior of selected cosmetic ra...
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In this study, a number of computed or chromatographically measured (RP-18 thin-layer chromatography [TLC]) descriptors are presented. The relationships between these descriptors and the observed (BBobs) and calculated (B2) BBB bioavailability were studied by stepwise multiple regression analysis and discriminant function analysis on a group of 34 compounds of diverse structures. Useful models of the blood—brain distribution given by the equations: BBobs = −1.19 + 2.05 B2 + 3.89 RF − 62.31 RF/PS...
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Abstract 211 compounds containing a benzodiazepine moiety ( BZD ) and belonging to 4 groups of different biological activity ( H - inhibitors of reverse transcriptase of HIV-I virus, A - antiarrhythmic agents, G - ligands of benzodiazepine receptor in GABAergic system and C - cholecystokinin receptor antagonists) were subjected to structure–activity relationship ( SAR ) analysis. SAR investigations of all 211 BZD were based on Discriminant Function Analysis ( DFA ) of physicochemical data connec...
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The lipophilicities of 22 selected sunscreens, preservatives, and vitamins used in topical skin products were measured by thin-layer chromatography. Lipophilicity was calculated in silico from the sunscreen molecular structures and compared to the experimental octanol/water partition coefficients found in the literature. The retention of the compounds was investigated on an RP-18 stationary phase with mobile phases consisting of water and one of six organic modifiers (dioxane, tetrahydrofuran, a...
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The properties relevant to pharmacokinetics and pharmacodynamics of four series of synthesized s-triazine derivatives have been studied by Quantitative structureretention relationship (QSRR) approach. The chromatographic behavior of these compounds was investigated by using reversed-phase high performance thin-layer chromatography (RP-HPTLC). Chromatographic retention (R M 0 ) was correlated with selected physicochemical parameters relevant to pharmacokinetics, i.e. ADME (absorption, distributio...
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Retention behaviour of molecules mostly depends on their chemical structure. Retention data of biologically active molecules could be an indirect relationship between their structure and biological or pharmacological activity, since the molecular structure affects their behaviour in all pharmacokinetic stages. In the present paper, retention parameters (R M 0 ) of biologically active 1,2-O-isopropylidene aldohexose derivatives, obtained by normalphase thin-layer chromatography (NP TLC), were cor...
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Abstract The rational preselection of drug candidates includes also correlation between physico-chemical properties (lipophilicity, as the key one) and pharmacokinetic properties, as well as pharmacodynamic activity. Lipophilicity can be determined alternatively by chromatographic methods. Chromatographic behavior of nineteen newly synthesized derivatives of 16-cyano-16,17-seco-5-androstene has been studied by reversed-phase and normal-phase thin-layer chromatography (RP- and NP-TLC). Commercial...
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Several chromatographic parameters (RM0 and S obtained from RP-18 TLC with methanol—pH 7.4 phosphate buffer mobile phases by extrapolation to zero concentration of methanol; Rf and RM obtained from RP-18 TLC with acetonitrile—pH 7.4 phosphate buffer 70:30 v/v as a mobile phase) and calculated molecular descriptors (molecular weight—MW; molar volume—VM; polar surface area—PSA; total count of nitrogen and oxygen atoms—(N+O); H-bond donor count—HD; H-bond acceptor count—HA; distribution coefficient...
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