Heterocycles 52: The Drug-Likeness Analysis of Anti-Inflammatory Thiazolo[3,2-b][1,2,4]triazole and Imidazo[2,1-b][1,3,4]thiadiazole Derivatives.

Lipophilicity, a significant physicochemical parameter of bioactive molecules, along with absorption, distribution, metabolism, excretion parameters and toxicity risk, was investigated for 32 thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives with anti-inflammatory potential. The experimental lipophilicity study was carried out by reversed-phase thin-layer chromatography in a binary isopropanol-water mobile phase, and the obtained results were compared with the theoretical lipophilicity parameters estimated by various computational methods. Strong correlations were found between the experimental retention factors and calculated partition coefficients. A modified Petra/Osiris/Molinspiration analysis was performed on the previously synthesized compounds, using SwissADME, Osiris and Molinspiration web tools. The predicted in silico parameters highlighted the most promising compounds as potential drug candidates. The compounds showed good gastrointestinal absorption, moderate activity according to the bioactivity score (values situated between -1.25 and -0.06), and a safe toxicity profile. The results obtained in this study will contribute to lipophilicity studies and other future studies focused on modulating new drug candidates starting from thiazolo[3,2-b][1,2,4]triazole and imidazo[2,1-b][1,3,4]thiadiazole derivatives, which are important heterocycles in medicinal chemistry.

Use of Secondary Metabolites Profiling and Antioxidant Activity to Unravel the Differences between Two Species of Nettle.

In recent years, the interest in natural remedies has increased, so it is important to analyze the plants widely distributed in nature but whose composition is little known. The main objective of the present work is to obtain information based on the profiles of secondary metabolites and antioxidant activity in Lamium album, a very widespread but little studied plant, with the aim of revealing the differences compared to Urtica dioica. First, the optimization of enzymatic extraction assisted by ultrasound was carried out by the Box-Behnken method. The optimized parameters were: concentration of the enzyme-3.3% cellulase, temperature-55 °C, and the extraction time-40.00 min. The efficiency was estimated based on the content of iridoids, the main class of secondary metabolites from Lamium album. Second, the secondary metabolites profiles of the nettle extracts were obtained by thin-layer chromatography using both normal and reverse phases and by RP-UHPLC. The antioxidant activity was evaluated using DPPH and ABTS+ radicals. The obtained results revealed significant differences between the two nettle species, both in terms of the phytochemical compounds, as well as the antioxidant activity, confirming the fact that Lamium album has a high potential to be used in phytomedicine.

Estimation of degradation kinetics of bioactive compounds in several lingonberry jams as affected by different sweeteners and storage conditions.

Lingonberry fruits are considered to play an important role in nutrition, as they comprise a variety of health-promoting components. Because of lingonberries seasonal availability and also due to their rapid degradation, their stability during processing is a continuous challenge for the food industry. Lingonberries are ideal fruits in making jam due to their natural deep reddish color, but recently, increased demand for low-calorie jams with alternative sweeteners has gained special attention. In this line, the objective of this study was to monitor the changes in anthocyanins, vitamin C, total phenolics, total reducing sugars and antioxidant capacity of several lingonberry jams formulated with different sweeteners (sucrose, fructose, erythritol, brown sugar, coconut sugar, stevia, saccharin). Due to the fact that storage conditions are important factors for jam quality, the jams were stored for 180 days at 4 °C and 25 °C (both under light and dark conditions). The rate constants (k) and the half time values (t1/2) of the degradation processes were determined and degradation kinetics was studied. For all analyzed conditions, first-order reaction kinetics was established for the degradation process of anthocyanins, whereas a second-order kinetic model described the degradation of the other compounds. Kinetic parameters showed that the stability of the studied compounds was highly influenced by the type of sweetener used in jam formulation. Total phenolics and antioxidants were best preserved in the presence of stevia, coconut sugar and fructose, whereas a destabilizing effect of erythritol on vitamin C and anthocyanins content during storage was observed. Among all the studied compounds, anthocyanins presented the fastest degradation, regardless storage conditions. The stability of studied compounds was higher at lower storage temperature (4 °C), while increasing the temperature at 25 °C and exposure to light determined higher rate of the degradation processes. The results provide useful information for understanding some bioactive compounds degradation in real foods, contributing to the development of new food products and providing information of commercial importance.

Effect of in vitro simulated gastrointestinal digestion on some nutritional characteristics of several dried fruits.

To provide new information on potential health benefits of dried fruits, the effects of in vitro digestion on minerals, total phenolics, total sugars and the antioxidant capacities were evaluated. For the first time, the bioaccessibility of these compounds during in vitro digestion was assessed by multivariate statistical analysis. Although the amount of all minerals decreased after digestion, moderate bioaccessibility was found, excepting Zn. The highest bioaccessibility of phenolics was obtained in prunes and the lowest in dates and cranberries. Total sugars content increased after in vitro digestion of dates, raisins and coconut, but decreased for cranberries, prunes and banana. The in vitro digestion led to an increase in the antioxidant capacity for the majority of dried fruits. The similarities/dis-similarities in pattern of analyzed parameters during digestion was revealed by heat map. Two-way joining cluster and principal component analysis were used to highlight the most relevant parameters in each digestion phase.

Application of HPTLC Multiwavelength Imaging and Color Scale Fingerprinting Approach Combined with Multivariate Chemometric Methods for Medicinal Plant Clustering According to Their Species.

In the current study, multiwavelength detection combined with color scales HPTLC fingerprinting procedure and chemometric approach were applied for direct clustering of a set of medicinal plants with different geographical growing areas. The fingerprints profiles of the hydroalcoholic extracts obtained after single and double development and detection under 254 nm and 365 nm, before and after selective spraying with specific derivatization reagents were evaluated by chemometric approaches. Principal component analysis (PCA) with factor analysis (FA) methods were used to reveal the contribution of red (R), green (G), blue (B) and, respectively, gray (K) color scale fingerprints to HPTLC classification of the analyzed samples. Hierarchical cluster analysis (HCA) was used to classify the medicinal plants based on measure of similarity of color scale fingerprint patterns. The 1-Pearson distance measurement with Ward's amalgamation procedure proved to be the most convenient approach for the correct clustering of samples. Data from color scale fingerprints obtained for double development procedure and multiple visualization modes combined with appropriate chemometric methods proved to detect the similar medicinal plant extracts even though they are from different geographical regions, have different storage conditions and no specific markers are individually extracted. This approach could be proposed as a promising tool for authentication and identification studies of plant materials based on HPTLC fingerprinting analysis.

Application of Inductively Coupled Plasma Spectrometric Techniques and Multivariate Statistical Analysis in the Hydrogeochemical Profiling of Caves-Case Study Cloșani, Romania.

The aim of the study was to develop the hydrogeochemical profiling of caves based on the elemental composition of water and silty soil samples and a multivariate statistical analysis. Major and trace elements, including rare earths, were determined in the water and soil samples. The general characteristics of water, anions content, inorganic and organic carbon fractions and nitrogen species (NO3- and NH4+) were also considered. The ANOVA-principal component analysis (PCA) and two-way joining analysis were applied on samples collected from Cloșani Cave, Romania. The ANOVA-PCA revealed that the hydrogeochemical characteristics of Ca2+-HCO3- water facies were described by five factors, the strongest being associated with water-carbonate rock interactions and the occurrence of Ca, Mg and HCO3- (43.4%). Although organic carbon fractions have a lower influence (20.1%) than inorganic ones on water characteristics, they are involved in the chemical processes of nitrogen and of the elements involved in redox processes (Fe, Mn, Cr and Sn). The seasonal variability of water characteristics, especially during the spring, was observed. The variability of silty soil samples was described by four principal components, the strongest influence being attributed to rare earth elements (52.2%). The ANOVA-PCA provided deeper information compared to Gibbs and Piper diagrams and the correlation analysis.

Multivariate color scale image analysis - Thin layer chromatography for comprehensive evaluation of complex samples fingerprint.

A chemometric evaluation of the information provided by different color scale fingerprints in thin layer chromatographic analysis of complex samples is proposed for the correct classification of a set of medicinal plant extracts. The fingerprints of the samples were acquired on HPTLC Silica gel 60 F254 and HPTLC Silica gel 60 plates using multiple levels of visualization under UV light. Images processing on red (R), green (G), blue (B) and respectively grey (K) color scale selection was used in order to evaluate the complete chromatographic profile of the extracts. Combination of Principal Component Analysis (PCA) and Factor Analysis (FA) method was applied in order to reveal the individual contribution of each color scales in the analysis of chromatographic fingerprints. The suggested technique provides an applicable strategy to screen for efficacy-associated color scale for grouping/classification of the extracts exploiting the information provided by HPTLC fingerprints. The principal component analysis and linear discriminant analysis (PCA-LDA) method was applied for the evaluation of numerical data provided by color scale fingerprints digitization and for samples classification. A correct classification of the analyzed extracts according to the plants phylum was revealed by color scale fingerprints analysis. The proposed methodology could be considered as a promising tool with future applications in plant material investigations even from the taxonomic perspective classification.

Heterocycles 51: Liphophilicity investigation of some thiazole chalcones and aurones by experimental and theoretical methods.

Reversed-phase thin-layer chromatography and reversed-phase high-performance liquid chromatography were used for lipophilicity determination of a library of 30 thiazole chalcones and aurones previously synthetized in our laboratory. The experimental lipophilicity data have been compared with theoretical lipophilicity parameters estimated by various computational methods. Good correlations between the experimental and calculated lipophilicity parameters have been found for both investigated classes of compounds. Correlations between the lipophilicity of the thiazole chalcones and aurones and their antiproliferative activity were discussed. The methodologies and data gathered in this study will contribute to the lipophilicity studies of chalcones and aurones derivatives, two important classes of compounds in medicinal chemistry.

A comprehensive classification of edible oils according to their radical scavenging spectral profile evaluated by advanced chemometrics.

A comprehensive study concerning the characterization and classification of 30 cold-pressed edible oils according to their UV-Vis spectra and radical scavenging profiles using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay is presented. Considering the principal component analysis (PCA) and fuzzy-principal component analysis (FPCA) loadings profiles, the characteristic spectral regions with a significant influence in oil samples classification were identified and associated with characteristic factors in each group. Much more, the oils with high antiradical capacity were revealed. The scores corresponding to the first principal component and the canonical scores corresponding to the first discriminant function derived from radical scavenging spectral profiles allowed a relevant classification of oils in well-defined groups associated with their high, medium and low radical scavenging capacity. The FPCA-LDA method applied on DPPH radical scavenging spectral profiles of edible oils appeared to be the most efficient method with a correct classification rate of 96.7%.

Classification of Romanian medicinal plant extracts according to the therapeutic effects using thin layer chromatography and robust chemometrics.

Thin layer chromatography in combination with image analysis and advanced chemometric methods were successfully used to classify the medicinal herbs according to their therapeutic effects and usage. The investigations were conducted using two types of plates (HPTLC Silica gel 60 and HPTLC Silica gel 60 F254) which were evaluated in UV light at 254 and 365 nm. The holistic evaluation of the numerical data corresponding different image processing channels (blue, grey, red, green) was performed by employing appropriate multivariate methods: hierarchical cluster analysis (HCA), principal component analysis (PCA), fuzzy principal component analysis (FPCA) and linear discriminant analysis (LDA) applied to the first relevant principal components. The results obtained by applying LDA method indicate a highly accurate separation of the medicinal herbs within the four groups, in good agreement with therapeutic effects and usage. According to this classification, the best image processing channels were identified for each of the investigated HPTLC plates: blue channel for HPTLC Silica gel 60 F254 (with 92.9% percent of discrimination in case of PCA and FPCA) and respectively red channel for HPTLC Silica gel 60 (with 93.9% percent of discrimination in case of FPCA). The 2D and 3D score scatterplots illustrate also the accurate and reliable discrimination between the four distinct groups.

Influence of Mixed Additives on the Physicochemical Properties of a 5.25% Sodium Hypochlorite Solution: An Unsupervised Multivariate Statistical Approach.

INTRODUCTION: This article reports for the first time the effects of multiple additives (polyethylene glycol 400, Triton X-100, benzalkonium chloride, and ethyl formate) on the surface tension, pH, and viscosity of 5.25% sodium hypochlorite (NaOCl) irrigant solution. Advanced statistical approaches based on unsupervised multivariate analysis (cluster analysis and principal component analysis) were used to quantify the variability of the physicochemical properties of the modified NaOCl solution for the first time in dentistry. METHODS: Solutions of 5.25% NaOCl were modified with multiple additives in various concentrations, physicochemical parameters were measured at 22°C and 37°C, and the results were statistically analyzed to group the solutions and reveal the effects of additives. RESULTS: Cluster analysis and principal component analysis revealed that pH and surface tension were the significant parameters (P < .05) for grouping the modified solutions. Four principal components, accounting for 90.6% of the total variance, were associated with flow characteristics (37.3%) determined by polyethylene glycol; the wetting property (22.5% and 10.5%), which was dependent on cationic and nonionic surfactant; and the antimicrobial effect (20.3%) influenced by ethyl formate. Varimax rotation of the principal components showed that the cationic surfactant (benzalkonium chloride) had significantly decreased surface tension compared with the nonionic surfactant (Triton-X). Although ethyl formate was introduced as an odor modifier, it had a significant effect on pH decrease and the occurrence of effervescence with O2 and hypochlorous acid release. CONCLUSIONS: The statistical results revealed that the 5.25% NaOCl irrigant solution should be modified with a mixture of 0.1% benzalkonium chloride, 1% ethyl formate, and 7% polyethylene glycol for obtaining a low pH and low surface tension.

Thin-layer chromatography--an image-processing method for the determination of acidic catecholamine metabolites.

A sensitive and convenient method for acidic catecholamine metabolites (including homovanillic acid, vanillylmandelic acid, 3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylacetic acid) determination was developed based on thin-layer chromatography and image-processing analysis. The metabolites were separated without a prederivatization step using reversed phase RP-18W high-performance plates. The mobile phase composition, detection, and quantification conditions were systematically investigated through several trials. The reaction with 2,2-diphenyl-1-picrylhydrazyl radical allowed specific detection of acidic catecholamine metabolites with a high sensitivity and a wide linear range. The limit of detection and the limit of quantification were in the range of 13-103 and 18-120 ng/spot, respectively, in all cases. Mean recoveries determined were in the range 95-106% for all of the investigated compounds. The proposed method allowed rapid simultaneous determination of acidic catecholamine metabolites from spiked human urine sample.

Heterocycles 33: lipophilicity of a new class of thioethers estimated by reversed-phase thin-layer chromatography and different computational methods.

The retention behavior for a series of new polyheterocyclic compounds containing azolic rings (1,3-thiazole, 1,2,4-triazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole) has been investigated using reversed-phase thin-layer chromatography. Different approaches and computational methods were employed to evaluate their lipophilicity indices derived from chromatographic parameters. The obtained experimental results were correlated with various lipophilicity indices estimated via different computer software and internet websites. A strong correlation between experimental and computed results was observed. Furthermore, the lipophilicity parameters obtained by applying principal component analysis divided the investigated compounds into four groups according to their structural similarities.

Lipophilicity of amine neurotransmitter precursors, metabolites and related drugs estimated on various TLC plates.

The retention behavior for a series of amine neurotransmitters, their precursors, metabolites and structurally related drugs has been investigated in reversed-phase thin-layer chromatography using RP-18, RP-8, RP-2, CN and Diol stationary phases and mixtures of phosphate buffer and methanol as mobile phase. According to the computed lipophilicity of the neutral form of the investigated compounds, the most lipophilic compound is dobutamine (log P(N) = 3.78), while the less lipophilic is norepinephrine (log P(N) = -0.14). The experimental results also show dobutamine as the most lipophilic compound in the case of RP-18 and CN stationary phases (RM0(RP-18) = 1.58 and RM(CN) = 1.21), while RP-8 indicates norepinephrine as the less lipophilic one (RM0(RP8) = -0.70). Both the theoretical computation and the experimental data revealed that only one ionic form of the compounds prevails in the used chromatographic conditions. In addition, the evaluation of the experimental results showed that a similar chromatographic behavior could be assumed in the case of RP-18, RP-8 and CN stationary phases. Moreover, the mRM (mean of the RM values) and PC1/RM (scores of the first principal component) experimental lipophilicity indices showed a high correlation with the computed lipophilicity indices.

Comprehensive evaluation of antioxidant activity: a chemometric approach using principal component analysis.

A novel chemometric approach is described for evaluating the radical scavenging activity of biogenic amine related compounds by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) procedure and principal component analysis (PCA) tool. By a comprehensive chemometric investigation of variations in the radical scavenging profiles provided by the full-range UV-Vis spectra for different test duration and different relative concentrations (different molar ratio - [AH]/[DPPH]) of the investigated compounds, new antioxidant activity evaluation parameters were proposed. The new proposed parameters (PC1, mPC1, maxPC1) are in good agreement with the reference DPPH results (% RSA and IC50 derived from the reference DPPH test), obtained for the investigated amines and reference antioxidants. Much more, the PCA profiles are better patterns for the comprehensive characterization of radical scavenging activity of compounds, allowing visualization of complex information by a simple graphical representation and underlying the (dis)similarity of compounds related both to the reaction kinetics and compounds concentration.

High sensitive and selective HPTLC method assisted by digital image processing for simultaneous determination of catecholamines and related drugs.

A highly sensitive and selective thin layer chromatographic (TLC) method was developed for simultaneous determination of catecholamines and their related drugs using a new detection method and digital image processing of chromatographic plates. For the quantitative evaluation of the investigated compounds, the chromatographic separation was followed by spraying the plate with 0.02% solution of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in ethanol. The BioDit Thin Layer Chromatography (TLC) Scanner device and advanced specific software (ImageDecipher-TLC, Sorbfil TLC Videodensitometer and JustTLC) were used for the detection and quantification of chromatographic spots. For an accurate determination, the RGB colored images of the bright-white spots detected against a purple background were inverted and processed after their conversion into green scale. The results showed a strongly linear correlation between area (R(2)>0.99) and volume (R(2)>0.99) of spots and concentration of investigated compounds in all cases. The limit of detection (LOD) and the limit of quantification (LOQ) were below 49.3 ng/spot and 69.6 ng/spot respectively in all cases. The evaluation of the method was performed using different pharmaceutical samples spiked with the investigated amines and validated with respect to accuracy and precision.

Chromatographic lipophilicity determination using large volume injections of the solvents non-miscible with the mobile phase.

A new perspective in the lipophilicity evaluation through RP-HPLC is permitted by analysis of the retention factor (k) obtained by injecting large volumes of test samples prepared in solvents immiscible with mobile phase. The experiment is carried out on representative groups of compounds with increased toxicity (mycotoxins and alkaloids) and amines with important biological activity (naturally occurring monoamine compounds and related drugs), which are covering a large interval of lipophilicity. The stock solution of each compound was prepared in hexane and the used mobile phases were mixtures of methanol or acetonitrile and water, in suited volume ratio. The injected volume was between 10 and 100 µL, while the used stationary phases were RP-18 and RP-8. On both reverse stationary phases the retention factors were linearly decreasing while the injection volume was increasing. In all cases, the linear models were highly statistically significant. On the basis of the obtained results new lipophilicity indices were purposed and discussed. The developed lipophilicity indices and the computationally expressed ones are correlated at a high level of statistical significance.

Comprehensive evaluation of lipophilicity of biogenic amines and related compounds using different chemically bonded phases and various descriptors.

The retention behavior for a series of biogenic amines and related sympathomimetic drugs has been investigated in reversed-phase thin-layer chromatography using RP-2, RP-8, RP-18W, and Diol stationary phase and mixtures of phosphate buffer (pH = 7.10) and methanol in different proportions as mobile phases. Several methodologies like arithmetic mean of experimental retention values, extrapolation to zero methanol concentration procedure and principal component analysis were applied to retention data values (R(M)) in order to determine relevant parameters (mean of R(M) - mR(M), R(M0), and scores corresponding to the first principal component - PC1/R(M) respectively) encoding information on the lipophilic behavior of compounds. High similarities in lipophilicity behavior of investigated amines were highlighted by mR(M) and PC1/R(M) lipophilicity indices for all of the studied stationary phases. The experimental results were compared with some computed lipophilicity parameters expressed as distribution coefficients at working pH (logD), partition coefficients (logP(N), logP(I), and diff(logP(N-I))) concerning both neutral and fully protonated species and difference between both species, and also with various lipophilicity values (logP) generated by different commonly used software. Significant correlations were observed between the experimental lipophilicity indices mR(M) respectively PC1/R(M) and diff(logP(N-I) ) values in all cases.

Prediction of pesticides chromatographic lipophilicity from the computational molecular descriptors.

Quantitative structure-property relationship models were developed for the prediction of pesticides and some PAH compounds lipophilicity based on a wide set of computational molecular descriptors and a set of experimental chromatographic data. The chromatographic lipophilicity of pesticides has been evaluated by high-performance liquid chromatography (HPLC) using different chemically bonded (C18, C8, CN and Phenyl HPLC columns) stationary phases and two different organic modifiers (methanol and acetonitrile, respectively) in the mobile phase composition. Through a systematic study, by using the classic multivariate analysis, several quantitative structure-property/lipophilicity multi-dimensional models were established. Multiple linear regression and genetic algorithm for the variable subset selection were used. The internal and external statistical evaluation procedures revealed some appropriate models for the chromatographic lipophilicity prediction of pesticides. Moreover, the statistical parameters of regression and those obtained by applying t-test for the intercept (a(0)) and for the slope (a(1)) in order to evaluate relationship between experimental and predicted octanol-water partition coefficients in case of the test set compounds, revealed two statistically valid models that can be successfully used in lipophilicity prediction of pesticides.

Modeling of chromatographic lipophilicity of food synthetic dyes estimated on different columns.

The retention behavior of some food synthetic dyes has been studied by RP-HPLC on chemically bonded C18, C8, C16 and CN stationary phases. Using methanol-ammonium acetate (0.08 mol/L, pH=6.76) as mobile phase, a linear behavior of retention parameters throughout the methanol fraction variance was obtained in all cases (r>0.99). The patterns of chromatographic behavior of the compounds illustrate high similarities between the C18, C8 and C16 columns, respectively. Highly significant correlations were obtained between experimental lipophilicity indices log k(w) and phi(0) estimated on C18 and C8 stationary phases and some computed log P-values. An extensive investigation made for quantitative structure-property (lipophilicity) relationships of studied dyes, using descriptors from Dragon software, multiple linear regression and genetic algorithm, revealed that the molecular descriptors appearing in the best models combine 2-D and 3-D aspects of the molecular structure. The most significant descriptors can be classified as radial distribution function, GETAWAY (autocorrelation), 3D-MoRSE signal, Burden eigenvalues and edge adjacency descriptors.