Application of chemometrics for identification of chemical constituents of essential oils of importance for biological activities of selected aromatic lamiaceae species

Essential oils (EOs) extracted from natural products are made up of large number of chemical constituents. Being natural mixtures of very complex nature, essential oils may consist of about 20-60 components at quite different concentrations. Essential oils are characterized by two or three major components being present at fairly high concentrations (20-70%) in comparison to other components that are present in trace amounts. From that reason one plant can provide a pool of chemical ingredients that cause a whole range of activities. The present paper analyzes the activities in the space of the chemical constituents of EOs of 7 medicinal plants from Lamiaceae family known as peppermint, oregano, thyme, rosemary, sage, basil and lemon balm. The hierarchical clustering analysis (HCA) was applied to explore the similarities and dissimilarities between the 7 Lamiaceae herbs, and chemical constituents of their EOs together with their antioxidant and antibacterial activity. More in-depth examination of the data was achieved by color map. HCA indicated the uniqueness of each essential oil considered. The high content of certain compounds, as well as the unique presence of other chemical constituents were identified for each EO. HCA grouped the studied EOs into two clusters: one with peppermint, oregano and thyme, and the other with rosemary and sage, while basil and lemon balm were non-clustered

QSRR study of β-tetralino-spiro-5-hydantoin derivatives

In recent years spiro compounds have attracted significant interest due to their unique conformational features and their structural implications on biological systems. Since spiro compounds contain two rings with only one shared atom have a good balance between conformational restriction and flexibility, makes them adaptable to many biological targets. Therefore, knowledge of their interactions in aqueous systems is of crucial importance for the understanding of biological response and hence the initial step for the selection of the compound for the drug candidate. In this poster presentation the retention data for two series of spiro compounds derivatives of β-tetralino-spiro-5-hydantoins with a 4-substituted benzyl group or a 2-(4- substituted phenyl)-2-oxoethyl group in the position 3 (structures presented in Figure 1) were investigated. The attention of this work will be focused on the evaluation of chromatographic lipophilicity parameters determined by means of reversed-phase thin layer chromatography (RP-TLC) and reversed phase high-performance liquid chromatography (RP-HPLC). Principal Component Analysis (PCA) will be used in order to find similarities and differences among the investigated compounds, their retention data and structural parameters relevant for the activity

Correlation between retention constants obtained in reversed-phase liquid chromatography and partition coefficients of some benzimidazole derivatives

Several calculation procedures for log P values based on the fragmental and atomic contributions are compared with experimental reversed-phase liquid chromatography (RPLC) retention constants of benzimidazole derivatives. The RPLC experiments were performed on HPLC comerrcially available LiChrosorb RP(-18 column with binary solvent mixtures of methanol-phosphate buffer (pH 7) as mobile phase. Retention constant log k0 was determined by the extrapolation method. Good correlaton was found between the retention constants log k0 and log P, as well as m and log P of the compounds investigated

A comparative study of chromatographic lipophilicity and bioactivity parameters of selected spirohydantoins

In this study, lipophilicity of 21 cycloalkylspiro-5-hidantoins was assessed. The overall goal of lipophilicity evaluation is preliminary investigation which should result in a decrease of the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity assessment was done by reversed-phase thin-layer chromatography and in silico methods. Chromatographic analyses were performed on C-18 modified thin-layer of silica gel with a two-component mobile phase consisting of water and organic solvent (acetonitrile, acetone, dioxane, or tetrahydrofuran) in different ratios. The chromatographic lipophilicities (R (M) (0)) were discussed and compared with computational log Ps calculated with various algorithms as well as in silico ADMET descriptors using linear regression and multivariate approach (hierarchical cluster analysis and principal component analysis). A high correlation was obtained between R (M) (0) values and calculated log P indicating a strong relationship between the variables. Multivariate data analysis enabled the comparison of the chemical structures, lipophilicity, pharmacokinetic predictors and toxicity of the investigated compounds

Influence of the mobile-phase modifier on the retention of some para-substituted amides; Correlation with compound lipophilicity

The chromatographic behavior of Para-substituted amides of alpha-phenylacetic, benzoic, propanoic, and 2,2-dimethylpropanoic acid has been studied in reversed-phase thin-layer chromatography on silica gel impregnated with paraffin oil. Mobile phases used were acetone-water, methanol-water, and dioxane-water. R-M(0) values were calculated by linear extrapolation of retention to 0% organic modifier for each mobile phase. The relationships between R-M(0) Values obtained with different organic modifiers in the mobile phases are discussed. C-0 values were obtained from the slopes and intercepts of linear relationships between retention and volume fraction of modifier. Correlation between partition coefficient, log P, and R-M(0) and between log P and C-0 was examined. Results show that C-0 is a better measure of the lipophilicity of the amides than R-M(0)

The retention behavior of some anilides on unconventional TLC supports

The TLC retention behavior of formanilide and I substituted acetanilides on starch and cellulose layers has been studied using aqueous mobile phases with methanol, acetonitrile, acetone, and 1-propanol as modifiers, R-Mw values derived by linear extrapolation of the plot of R-M against volume fraction of organic modifier to 100% water are not dependent on the nature of the organic modifier, Correlation was observed between R-Mw values on starch and cellulose layers, Because R-M values are related to the partitioning of the solute molecules in the given system, they can be regarded as a measure of a solute's hydrophobicity, We correlated R-Mw values with the lipophilicity parameters, pi and logP; the quadratic equation fit the data well, Multiple regression analyses was, furthermore, successfully applied with pi, sigma, and HD as independent variables? suggesting that the electronic properties and hydrogen bonding of the substituent participate in the retention mechanism

Normal- and reversed-phase chromatography of para-substituted propanoic acid Amides

The chromatographic behavior of newly synthesized para-substituted propanoic acid amides has been studied in normal- and reversed-phase thin-layer chromatography. The retention mechanism on different TLC supports was investigated. The retention constants determined for the amides are discussed in terms of the physicochernical properties of the solute and the stationary and mobile phases. R-M,R-w, derived by extrapolation from retention in reversed-phase chromatography, was correlated with hydrophobic parameters pi and log P, calculated by the Rekker fragmental method and by use of the commercial program ACD/log P

Structure-Retention Relationship Study of HPLC Data of Antiepileptic Hydantoin Analogues

In the study, 18 antiepileptic hydantoin analogues were investigated by means of reversed-phase HPLC on C-18 stationary phase and eluent acetonitrile-water. Quantitative structure-retention relationship (QSRR) study has been applied in order to understand factors that affect the retention which is closely correlated to the activity (ED50 values). To overview the compounds for similarities and dissimilarities principal component analysis (PCA) has been applied. Six multiple linear regression models based on the most relevant descriptors were developed. Descriptors for MLR were selected according to variable importance calculated by partial least squares (PLS) analysis. Besides ALOGP the most important is aromatic ratio for mobile phases with more than 45% of acetonitrile, as well as electrotopological states when the % of acetonitrile is less than 40%. High agreement between experimental and predicted retention, obtained in the validation procedure, indicated the good quality of the derived QSRR models. For individual linear models, cross-validation squared correlation coefficients (Q(2)) ranging from 0.697 to 0.837 were obtained. The residual values (difference between observed and calculated) agreed well within experimental error. Additionally, models were compared in terms of the smallest residual value by recently developed method of ranking based on the sum of ranking differences (SRD)

Multivariate evaluation of the correlation between retention data and molecular descriptors of antiepileptic hydantoin analogs

Molecular properties relevant to pharmacokinetics of two sets of newly synthesized hydantoin derivatives based on two well-known drugs (Nirvanol and Phenytoin) were studied. Properties under consideration were either determined empirically by reversed-phase high-performance thin-layer chromatography or calculated by the use of established theoretical medicinal chemistry/drug design software. These properties represent selected structural features of analytes, which affect their processes of absorption, distribution, metabolism, excretion, and toxicity. Principal component analysis was used to visualize the differences between six mobile phase modifiers used as well as similarities between 24 analyzed compounds. To find appropriate quantitative relationships between RM, W for the tested compounds and molecular descriptors, stepwise regression, partial least squares (PLS), and robust PLS were used. The best results were obtained with robust PLS

Chemometric Study of the Antiproliferative Activity of Some New Hydantoin Derivatives: Assessment of Activity and Chromatographic Lipophilicity Data

Cancer is the major health problem affecting the mankind of today. Most of the drugs used in traditional chemotherapy are very limited and the discovery of novel, more active, more selective and less toxic ones is still very intensive. A chemometric approach was applied in the study of antiproliferative activity against human colon cancer and breast cancer as well as in the study of lipophilicity of 3-(4-substitutedbenzyl)-5-ethyl-5-phenyl- and 3-(4-substituted benzyl)-5,5-diphenylhydantoins. Hierarchical clustering analysis (HCA) shows that the investigated hydantoins have higher antiproliferative activity against human breast cancer cells than against human colon cancer cells. However, some hydantoins at the highest applied concentration reverse antiproliferative effect, higher against the human colon cancer cells and lower against human breast cancer cells. Principal component analysis (PCA) gives better insight into the activity of hydantoins related to their structural changes. It distinguishes more active compounds from the less active ones according to various criteria. Generally, more lipophilic 5,5-diphenylhydantoins exhibit a higher antiproliferative activity comparing to less lipophilic 5-ethyl-5-phenylhydantoins. Also, a substituent attached to benzyl moieties affects the activity additionally. The activity is particularly pronounced for compounds with cyano, methyl, chloro and bromo group. Halogen substituent were superior in antiproliferative capacity particularly in the series of 5,5-diphenylhydantoins