CHROMATOGRAPHIC PARAMETERS IN THE ASSESSMENT OF LIPOPHILICITY AND TOXICITY OF THIOCARBOHYDRAZONE DERIVATIVES

Abstract

In recent years, the number of studies focused on the design and synthesis of compounds with bio­logical and pharmacological potential has increased significantly. Special attention has been given to molecules with antitumor activity, including thiosemicarbazones and their homologues, thiocarbohydrazones. Since drug development is a complex, lengthy, and expensive process, its optimization in early stages often relies on the application of Quantitative Structure–Activity Relationship (QSAR) approach. By selecting appropriate molecular descriptors, it is possible to quantify the impact of structural modifications on compound’s biological activity prior to synthesis, thus reducing the need for extensive experimental work. Lipophilicity as key QSAR descriptor, was determined for thiocarbohydrazones by using a hybrid approach – computationally, through appropriate software tools (logP as a standard measure of lipophilicity), and experimentally, by reversed-phase thin-layer chromatography (chromatographic parameters RM0 and m). The results indicated that the nature of the substituent had a greater effect on the chromatographic behavior of thiocarbohydrazones than the applied organic modifier. The correlation between chromatographically and computationally determined lipophilicity values, as well as the acute toxicity parameters (EC50), was assessed by linear regression analysis. The obtained models showed satisfactory predictive performance.
Keywords: thiocarbohydrazones, chromatography, lipophilicity, toxicity.