A Comparative Study of the Lipophilicity of Metformin and Phenformin

The results presented in this paper confirm the beneficial role of an easy-to-use and low-cost thin-layer chromatography (TLC) technique for describing the retention behavior and the experimental lipophilicity parameter of two biguanide derivatives, metformin and phenformin, in both normal-phase (NP) and reversed-phase (RP) TLC systems. The retention parameters (RF, RM) obtained under different chromatographic conditions, i.e., various stationary and mobile phases in the NP-TLC and RP-TLC systems, were used to determine the lipophilicity parameter (RMW) of metformin and phenformin. This study confirms the poor lipophilicity of both metformin and phenformin. It can be stated that the optimization of chromatographic conditions, i.e., the kind of stationary phase and the composition of mobile phase, was needed to obtain the reliable value of the chromatographic lipophilicity parameter (RMW) in this study. The fewer differences in the RMW values of both biguanide derivatives were ensured by the RP-TLC system composed of RP2, RP18, and RP18W plates and the mixture composed of methanol, propan-1-ol, and acetonitrile as an organic modifier compared to the NP-TLC analysis. The new calculation procedures for logP of drugs based on topological indices 0χν, 0χ, 1χν, M, and Mν may be a certain alternative to other algorithms as well as the TLC procedure performed under optimized chromatographic conditions. The knowledge of different lipophilicity parameters of the studied biguanides can be useful in the future design of novel and more therapeutically effective metformin and phenformin formulations for antidiabetic and possible anticancer treatment. Moreover, the topological indices presented in this work may be further used in the QSAR study of the examined biguanides.

Development of TLC Chromatographic-Densitometric Procedure for Qualitative and Quantitative Analysis of Ceftobiprole

Currently, there is still a need for broad-spectrum antibiotics. The new cephalosporin antibiotics include, among others, ceftobiprole, a fifth-generation gram-positive cephalosporin, active against Staphylococcus aureus methicillin agonist (MRSA). The main focus of the work was to optimize the conditions of ceftobiprole qualitative determination and to validate the developed procedure according to ICH guidelines. As a result of the optimization process, HPTLC Cellulose chromatographic plates as a stationary phase and a mixture consisting of ethanol:2-propanol: glacial acetic acid: water (4:4:1:3, v/v/v/v) as a mobile phase were chosen. The densitometric detection was carried out at maximum absorbance of ceftobiprole (λ = 232 nm). Next, the validation process of the developed procedure was carried out. The relative standard deviation (RSD) for precision was less than 1.65%, which proves the high compatibility of the results, as well as the LOD = 0.0257 µg/spot and LOQ = 0.0779 µg/spot values, which also confirm the high sensitivity of the procedure. The usefulness of the developed method for the stability studies of ceftobiprole was analyzed. Study was carried out under stress conditions, i.e., acid and alkaline environments, exposure to radiation imitating sunlight and high temperature (40–60 °C). It was found that cefotbiprole is unstable in an alkaline environment and during exposure to UV-VIS radiation. Moreover, the lipophilicity parameter, as a main physicochemical property of the biologically active compound, was determined using experimental and computational methods.

Evaluation of the Lipophilicity of New Anticancer 1,2,3-Triazole-Dipyridothiazine Hybrids Using RP TLC and Different Computational Methods

Two new anticancer-active 1,2,3-triazole-dipyridothiazine hybrids were evaluated for their lipophilicity using thin-layer chromatography (TLC) and computational methods. The experimental lipophilicity was evaluated with mobile phases (mixtures of TRIS buffer and acetone), exploiting a linear correlation between the retention parameter (RM) and the volume of acetone. The relative lipophilicity parameter (RM0) was obtained by extrapolation to 0% acetone concentration. This parameter was intercorrelated with a specific hydrophobic surface area (b) revealing two congeneric subgroups: hybrids of 1,2,3-triazole-2,7-diazaphenothiazines and 1,2,3-triazole-3,6-diazaphenothiazines. The parameter RM0 was converted into the absolute lipophilicity parameter logPTLC using a calibration curve prepared on the basis of compounds of known logP values. Triazole–dipyridothiazine hybrids turned out to be medium lipophilic with logPTLC values of 1.232–2.979. The chromatographically established parameter logPTLC was compared to the calculated lipophilic parameter logPcalcd obtained with various algorithms. The lipophilicity was correlated with molecular descriptors and ADME properties. The new triazole–dipyridothiazine hybrids followed Lipinski’s rule of five. The lipophilicity of these hybrids was dependent on the substituents attached to the triazole ring and the location of the azine nitrogen atoms.

The Application of CA and PCA to the Evaluation of Lipophilicity and Physicochemical Properties of Tetracyclic Diazaphenothiazine Derivatives

The subject of the study was 11 new synthetized tetracyclic diazaphenothiazine derivatives. Using thin-layer chromatography in a reverse phase system (RP-TLC), their RM0 lipophilicity parameter was determined. The mobile phase was composed of 0.2 M Tris buffer (pH = 7.4) and acetone (POCH S.A., Gliwice, Poland) in different concentrations. Using computer programs, based on different computational algorithms, theoretical values of lipophilicity (AClogP, ALOGP, ALOGPs, miLogP, MLOGP, XLOGP2, and XLOGP3) as well as molecular descriptors (molecular weight, volume of a molecule, dipole moment, polar surface, and energy of HOMO orbitals and LUMO orbitals) and parameters of biological activity: human intestinal absorption (HIA), plasma protein binding (PPB), and blood-brain barrier (BBB), were determined. The correlations between the experimental values of lipophilicity and theoretically calculated lipophilic values and also between experimental values of lipophilicity and values of physicochemical or biological properties were assessed. A certain relationship between structure and lipophilicity was found. On the other hand, the relationships between RM0 and physicochemical or biological properties were not statistically significant and therefore unusable. For all analysed values, an analysis of similarities and principal component analyses were also made. The obtained dendrograms for the analysis of lipophilicity and physicochemical and biological properties indicate the relationship between experimental values of lipophilicity and structure in the case of theoretical lipophilicity values only. PCA, on the other hand, showed that ALOGP, MLOGP, miLogP, and BBB and molar volume have the largest share in the description of the entire system. Distribution of compounds on the area of factors also indicates the connections between them related to their structure.

A structural framework of biologically active coumarin derivatives: crystal structure and Hirshfeld surface analysis

The relation between the lipophilicity parameter (log P) and the contribution of C–H⋯π interactions to the Hirshfeld surface has been investigated.

Correlation between the lipophilicity and antifungal activity of some benzoxazole derivatives

In the present work, a quantitative relationship between the lipophilicity and antifungal activity of some benzoxazole derivatives against Candida albicans was investigated by using QSAR (quantitative structure-activity relationship) analyses. The descriptors which describe numerically the lipophilicity, logP, were calculated using Chem-Office Software version 7.0. The linear correlation between the minimal inhibitory concentration (log1/cMIC) and lipophilicity descriptors was investigated. The best QSAR model predicting the antifungal activity of the investigated series of benzoxazole was developed. The results are discussed on the basis of statistical data. High agreement between theoretical and experimental inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on antifungal activity of this class of compounds, which can be very useful in the design of new biologically active molecules.

Quantitative structure-activity relationships to predict antibacterial effect of some benzimidazole derivatives

The antibacterial activity of some substituted benzimidazole derivatives against Gram negative bacteria Escherichia coli was investigated. The tested compounds displayed in vitro inhibitory activity and their minimum inhibitory concentrations were determined. Quantitative structure-activity relationship has been used to study the relationships between the antibacterial activity and lipophilicity parameter, logP. Lipophilicity parameters were calculated for each molecule by using CS Chem-Office Software version 7.0. Multiple linear regression was used to correlate the logP values and antibacterial activity of benzimidazole derivatives. The results are discussed on the basis of statistical data. The most acceptable QSAR model for prediction of antibacterial activity of the investigated series of benzimidazoles was developed. High agreement between experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on antibacterial activity of this class of compounds, thus simplifying design of new biologically active molecules.