QSRR modeling of lipophilicity of new spirohydantoin derivatives determined with various TLC systems.

A Quantitative structure-retention relationship (QSRR) analysis has been carried out on the chromatography parameters of lipophilicity of selected spirohydantoins. Multiple linear regression (MLR) was applied for construct the QSRR models. The chromatographic parameters of lipophilicity were determined by reversed-phase thin-layer chromatography. Chromatographic analyses were performed on C-18 modified silica gel with a two-component mobile phase consisting of water and protic organic solvent (ethanol, n-propanol, i-propanol, or t-butanol) in different ratios. QSRR models were built and for additional four aqueous mobile phases: acetone-water, acetonitrile-water, tetrahydrofuran-water, and 1,4-dioxane-water (results published before). In total, chromatographic lipophilicity parameters obtained for two types of organic solvents was subject of the QSRR. The predictive ability of each model was defined by an internal validation coefficient. The best QSRR model for predicting the chromatographic parameter of lipophilicity was obtained for tetrahydrofuran as an organic solvent.

QSAR characterization of new synthesized hydantoins with antiproliferative activity.

Hydantois have been identified as constituents of a number of pharmacologically active molecules. In the present study, we have examined in vitro antiproliferative activity against human colon cancer cell lines HCT-116 of three series of 3-(4-substituted benzyl)-hydantoins with various substituent attached in position 5 of the hydantoin ring. Since the investigated compounds have recently been synthesized and show antiproliferative activity, a good understanding of the properties of the potential drug responsible for their pharmacokinetics is an important goal for their further development. One of the important properties is lipophilicity. Lipophilicity has been assessed by reversed-phase liquid chromatography (high-performance thin-layer chromatography and high-pressure liquid chromatography) by means of direct and indirect (using calibration curve) methods. Chromatographic lipophilicity indices in addition to calculated logP values were compared by hierarchical cluster analysis. The linear solvation energy relationship approach was used to understand and compare the types and relative strength of the molecular interactions that occur in the chromatographic as well as in the n-octanol-water partitioning systems. Finally, correlation between in silico pharmacokinetic predictors and antiproliferative activity was examined. Preliminary quantitative structure-activity relationship modeling indicates that pharmacokinetic predictors capture only one-quarter of all chemical features that are important for antiproliferative activity itself. Among selected descriptors are chromatographic lipophilicity indices.

In Silico Study of Chromatographic Lipophilicity Parameters of 3-(4-Substituted Benzyl)-5-Phenylhydantoins.

New synthesized compounds, particularly those with biological activity, are potential drug candidates. This article describes experimental studies performed to estimate lipophilicity parameters of new 3-(4-substituted benzyl)-5-phenylhydantoins. Lipophilicity, as one of the most important molecular characteristics for the activity, was determined using the reversed-phase liquid chromatography (RP-18 stationary phase and methanol-water mobile phase). Molecular structures were used to generate in silico data which were used to estimate pharmacokinetic properties of the investigated compounds. The results show that generally, the investigated compounds attain good bioavailability properties. A more detailed analysis shows that the presence of a nitro, methoxy and tert-butyl group in the molecule is indicated as unfavorable for the oral bioavailability of hydantoins. Multivariate exploratory analysis was used in order to visualize grouping patterns among molecular descriptors as well as among the investigated compounds. Molecular docking study performed for two hydantoins with the highest bioavailability scores shows high binding affinity to tyrosine kinase receptor IGF-1R. The results achieved can be useful as a template for future development and further derivation or modification to obtain more potent and selective antitumor agents.