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  • Author or Editor: Elżbieta Brzezińska x
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Quantitative structure-activity relationships (QSAR) between H 1 -histaminergic activity and chromatographic data have been investigated for derivatives of 2-[2-(phenylamino)thiazol-4-yl]ethanamine, 2-(2-benzyl-4-thiazolyl)ethanamine, 2-(2-benzhydrylthiazol-4-yl)ethanamine, 2-(1-piperazinyl)benzothiazole, and 2-(hexahydro-1 H -1,4-diazepin-1-yl)benzothiazole. TLC was performed on normal-phase plates (silica gel 60F 254 ) impregnated with solutions of amino acid analogs (propionic acid, propionamide, and n -amylamine) and their mixtures, and with two mobile phases — these systems were selected as models of antagonistic interaction with the human histamine H 1 -receptor. Lipophilicity data were obtained for the compounds examined and used in the QSAR assays. Relationships between chromatographic data and biological activity were found by regression analysis. The correlations obtained in these NP TLC experiments were more significant than those obtained in experiments with RP2 TLC, because of optimum fitting of the chromatographic conditions to the lipophilicity of the solutes. All the chromatographic models proposed should facilitate pre-selection of new drug candidates. Significant correlation ( R 2 = 0.92−0.96) was obtained between p A 2 (H 1 ) values predicted for the compounds by the use of the best equations and the p A 2 (H 1 ) values obtained for the compounds from biological tests.

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A particularly rapid HPTLC method has been established for chromatographic separation and quantification of p -aminobenzoic acid (PABA) in complex dietary supplement tablets. After chromatography, PABA was determined by spectrodensitometry at 270 nm. PABA spots were then visualized by a novel staining procedure involving the Bratton-Marshall coupling reaction after spraying with 8-hydroxyquinoline in situ on the chromatographic plates. After visualization, spectrodensitometric analysis was repeated at 500 nm. Linearity, intermediate precision, sensitivity, accuracy, and precision were compared for both methods. Results from tablet analysis were verified with the modified Bratton-Marshall spectrophotometric procedure.

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A simple, rapid, and effective method for TLC separation of two EU-authorized UV filters octyl methoxycinnamate (OMC) and diethylamino hydroxybenzoyl hexyl benzoate (DHHB) on silica gel 60 is proposed. Separation conditions were optimized and cyclohexane-diethyl ether-acetone 15:1:2 (ν/ν) was used as mobile phase. Quantification of both filters on the same chromatographic plates was achieved by densitometric scanning in absorption-reflectance mode at 300 and 360 nm, respectively. The method enabled separation of other UV-absorbing ingredients commonly found in cosmetic sunscreen preparations, for example parabens or ethylhexyltriazone (ET). Good quality, linear calibration plots were generated over the range 200–2000 ng per spot both for OMC and DHHB. The method was validated.

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Quantitative structure-activity relationships (QSAR) between H 1 -histaminergic activity and chromatographic data have been investigated for derivatives of 2-[2-(phenylamino)thiazol-4-yl]ethanamine, 2-(2-benzyl-4-thiazolyl)ethanamine, 2-(2-benzhydrylthiazol-4-yl)ethanamine, 2-(1-piperazinyl)benzothiazole, and 2-(hexahydro-1 H -1,4-diazepin-1-yl)benzothiazole. TLC was performed on precoated silanized silica gel RP2 60F 254 plates impregnated with solutions of propionic acid, propionamide, and n -amylamine (used as amino acid analogs) and their mixtures, with two mobile phases — the systems were chosen as models of hH1R antagonistic interaction. Relationships between chromatographic and biological activity data were found by use of regression analysis. The correlations obtained for the thiazole and benzothiazole derivatives with H 1 -antihistamine activity (p A 2 (H 1 )) represent their interaction with all the proposed biochromatographic models (S1–S4). Some of the correlation equations obtained can be used to predict the pharmacological activity of new drug candidates. Lipophilicity data were obtained for the compounds and used in QSAR assays. The log P values of particular compounds are an extremely important indicator of this kind of activity.

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The relative lipophilicity of bioactive derivatives of 2-[1-(4-alkylpiperazinyl)]benzothiazoles, 2-[4-(1-alkyl)piperidinyl]benzothiazoles, 2-( N,N ’-dimethyl-1,2-ethanediamino)benzothiazoles, and 2-1-(4-aminopiperidinyl)benzothiazoles has been determined by reversed-phase thin-layer chromatography. R M values of these compounds were determined with acetone-buffer mobile phases and extrapolated to 100% aqueous conditions. The lipophilicity was also determined by using optimized structures of the investigated compounds based on quantum mechanical calculations of the chemical structures (HyperChem 7.0). The distribution coefficients of the examined compounds were determined by use of the calculated ‘correction for dissociation’ descriptor. A correction was made based on the dissociation constants of the compounds, which were determined spectrophotometrically. We present a method for calculation of partition coefficients for ionizable compounds at a given pH. This property can be useful in analysis of quantitative structure-activity relationships. The distribution coefficients and the actual partition coefficient (at pH 7.4) were calculated for benzothiazole derivatives and for other drugs with different structures. The validity of calculations was checked by comparison with available experimental partition and distribution coefficients.

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TLC separation of the UV filters avobenzone (AVO) and octocrylene (OCR) on RP-18 and silica gel 60 as stationary phases, with numerous mobile phases, revealed that these compounds have similar retention properties under almost all the chromatographic conditions investigated. Analysis of avobenzone in the presence of octocrylene may be achieved on silica gel 60 with cyclohexane-diethyl ether 1:1 (ν/ν) as mobile phase, at the selective wavelength 380 nm, at which octocrylene does not absorb (Method A). Analysis of octocrylene in the presence of avobenzone by the same method was, however, impossible because of insufficient chromatographic separation of AVO and OCR and overlap of the absorption ranges of AVO and OCR (with OCR peaks being obscured by those of AVO). An alternative separation strategy was proposed that proved successful for OCR in the presence of AVO. This involved chromatography on silica gel 60 with cyclohexane-piperidine 15:1 (ν/ν) as mobile phase (Method B). When these chromatographic conditions were used, retention of avobenzone changed substantially and OCR peaks became clearly visible. Spectrodensitometric scanning for OCR was then performed at 300 nm. Both methods were validated, and gave calibration plots of good linearity.

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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 R F − 62.31 R F/PSA + 0.290 log D (R 2 = 0.85, n = 24) and B2 = 4.06 − 1.61 HA − 1.95 HD + 105.49 R F/PSA (R 2 = 0.95, n = 34) were developed and validated. Models for discrimination between CNS+ and CNS− compounds were built on the basis of R F, R F/PSA, HD, and B2 descriptors. The diagnostic power of important parameters was evaluated by cluster analysis. Thirty-four compounds examined throughout this study were successfully assigned to two clusters: CNS+ and CNS−. Analysis of variances for 6 descriptors (HD, HA, R F, R F/PSA, DM, and B2) confirmed the conclusion that the parameters of good differentiating power are B2, HA, HD, R F/PSA ,and R F. The results of the chromatographic analysis proposed in this study (RP-18 TLC) are a source of valuable information on the ability of compounds to cross the BBB. This simple, inexpensive, and very rapid chromatographic technique may be used to assess the BBB permeability of compounds isolated or synthetized on a very small scale. The computed B2 descriptor is a convenient and readily available parameter useful also in the case of theoretical structures.

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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 raw materials (UV filters and preservatives) towards the BBB on the basis of the BBB permeability models developed in our earlier study, based on easily accessible RP-18 thin-layer chromatographic data and calculated molecular descriptors. The computed BBB permeability parameters B1 and B2 correlate with the chromatographic data (R F, R F/PSA) and calculated physicochemical descriptors usually associated with the BBB permeation (HA, Sa, DM, log D). The relationships between these values were developed by stepwise multiple regression analysis, validated, and found to explain 93–96% of the total variance. The models of the BBB permeation based on classification functions obtained previously from discriminant function analysis were used to assign the studied compounds to the groups of good (CNS+) or poor (CNS−) blood—brain barrier permeability, suggesting the inability of the majority of these compounds to cross the BBB. The universal character of BBB permeability models developed earlier was confirmed.

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