Teicoplanin-Modified HPLC Column as a Source of Experimental Parameters for Prediction of the Anticonvulsant Activity of 1,2,4-Triazole-3-Thiones by the Regression Models

Jolanta Flieger; Anna Orzeł; Anna Kowalska-Kępczyńska; Magdalena Pizoń; Hanna Trębacz; Dariusz Majerek; Tomasz Plech; Wojciech Płaziński

doi:10.3390/ma13112650

Teicoplanin-Modified HPLC Column as a Source of Experimental Parameters for Prediction of the Anticonvulsant Activity of 1,2,4-Triazole-3-Thiones by the Regression Models

Materials (Basel). 2020 Jun 10;13(11):2650. doi: 10.3390/ma13112650.

Authors

Jolanta Flieger¹, Anna Orzeł², Anna Kowalska-Kępczyńska³, Magdalena Pizoń¹, Hanna Trębacz⁴, Dariusz Majerek⁵, Tomasz Plech⁶, Wojciech Płaziński⁷

Affiliations

¹ Department of Analytical Chemistry, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.
² Faculty of Medicine, Medical University of Lublin, Aleje Racławickie 1, 20-059 Lublin, Poland.
³ Department of Biochemical Diagnostics, Medical University of Lublin, Staszica 16, 20-081 Lublin, Poland.
⁴ Chair and Department of Biophysics, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
⁵ Department of Applied Mathematics, University of Technology, Nadbystrzycka 38D, 20-618 Lublin, Poland.
⁶ Department of Pharmacology, Faculty of Nursing and Health Sciences, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.
⁷ Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239 Krakow, Poland.

Abstract

The cell membrane is a complex system that consists of lipids, proteins, polysaccharides, and amphiphilic phospholipids. It plays an important role in ADME processes that are responsible for the final pharmaceutical effects of xenobiotics (bioavailability, activity). To study drug-membrane interaction at the molecular level, several high-performance liquid chromatography (HPLC) membrane model systems have been proposed which are mimicking mainly its lipid character. The aim of this work was to study interactions of new synthesized antiepileptic compounds of 4-alkyl-5-(3-chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives with Chirobiotic column containing glycoprotein ligand attached to the silica matrix. The affinity of the analytes to immobilized glycoprotein ligand was examined chromatographically in reversed-phase mode. The thermodynamics of interactions between bioactive compounds and teicoplanin was studied in terms of the van't Hoff linear relationship ln k vs. 1/T in the range of 5-45 °C. Change in enthalpy (ΔH°), change in entropy (ΔS°) and change in Gibbs free energy (ΔG°) were estimated utilizing graphical extrapolation and interpolation methods. The density functional theory (DFT) approach and docking simulations were used to get the molecular interpretation and prove the obtained experimental results. Cross-correlations of chromatographic and thermodynamic parameters with non-empirical topological and quantum chemical indices suggest that the polarizability of analytes appears to be responsible for the interactions of the tested molecules with teicoplanin and, ultimately, their retention on the column. Experimental and theoretical parameters were subjected to statistical analysis using regression models. Partial least squares (PLS) regression model showed the usefulness of the experimentally measured parameter φ₀ (MeOH) to discriminate between anticonvulsant active and inactive 1,2,4-triazole-3-thione derivatives. Obtained results point out the usefulness of interaction of potential anticonvulsants with glycoprotein class of compounds to anticipate their activity.

Keywords: 1,2,4-triazole-3-thione derivatives; DFT results; docking simulation; phase ratio; phase transition; regression models; retention behavior; teicoplanin column; thermodynamic parameters; van’t Hoff relationship.