Chromatographic and Calculation Methods for Analysis of the Lipophilicity of Newly Synthesized Thiosemicarbazides and their Cyclic Analogues 1,2,4-Triazol-3-thiones

Anna M Hawrył,Milena A Niejedli,Mirosław A Hawrył,Łukasz P Popiołek,Ryszard S Świeboda

doi:10.5935/0103-5053.20150132

Abstract

This paper describes the evaluation of the lipophilicity of newly synthesized thiosemicarbazides and their cyclic analogues 1,2,4-triazol-3-thiones obtained using experimental and calculated methods. Previous studies have shown these compounds have antibacterial activity. The chromatographic behavior of analyzed compounds was studied by reversed phase high performance liquid chromatography (RP-HPLC) and reversed phase thin layer chromatography (RP-TLC). The aqueous mobile phases containing methanol were used in order to determine retention parameter (RM) and capacity factors (log k) of analyzed compounds. The lipophilicity parameters were obtained by linear extrapolation and they were compared with the calculated log P obtained using several software packages. The results indicate that both experimental chromatographic methods yielded similar results, and these methods are appropriate for determining the lipophilicity of analyzed compounds. High values of correlation coefficients between the log P values calculated using known algorithms (milogP, ALOGPs, AClogP, AlogP, MLOGP, KOWWIN, XLOGP2, XLOGP3) and the experimental data were obtained. Eight standard solutes with known log POW were analyzed under the same conditions as the tested substances in order to determine the log PHPLC and log PTLCparameters. A good correlation was obtained between log kw (or RMW) and the slope. All tested compounds were in agreement with the rule of five claims by Lipinski. The calculated log P values were experimentally confirmed (log PHPLC and log PTLC).

Highlights

Synthesis and confirmation of identity of studied thiosemicarbazide derivatives and their cyclic analogues 1,2,4-triazole-3-thiones were described early.[1]
Lipophilicity is a chemical affinity for the lipid and aqueous phases, and the measure is the ratio of the equilibrium concentration of the solute in the two-phase system consisting of two immiscible solvents non-polar and polar ones.[2,3,4]
The aim of this work is the comparison the log POW of thiosemicarbazide derivatives and their cyclic analogues 1,2,4-triazole-3-thiones, which can be used as potential drugs, determined by reversed phase high performance liquid chromatography (RP-HPLC) and RP‐TLC methods with the calibration curve technique with the log P values calculated using known algorithms.[24,25,31]

Summary

Introduction

Synthesis and confirmation of identity of studied thiosemicarbazide derivatives and their cyclic analogues 1,2,4-triazole-3-thiones were described early.[1]. It is well known that the biological activity of some substances is related to their lipophilicity. This parameter determines the bioavailability of the chemical compound and it has been important, in prediction of crossing biological barriers of drug molecules and its interactions with receptors. Lipophilicity is a chemical affinity for the lipid and aqueous phases, and the measure is the ratio of the equilibrium concentration (activity) of the solute in the two-phase system consisting of two immiscible solvents non-polar and polar ones.[2,3,4] For a long time, the distribution coefficient between n-octanol and water was used as

Objectives

Methods

Results