Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives

Abstract

Pseudothiohydantoin derivatives have a wide range of biological activities and are widely used in the development of new pharmaceuticals. Lipophilicity is a basic, but very important parameter in the design of potential drugs, as it determines solubility in lipids, nonpolar solvents, and makes it possible to predict the ADME profile. The aim of this study was to evaluate the lipophilicity of 28 pseudothiohydantoin derivatives showing the inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) using chromatographic methods. Experimentally, lipophilicity was determined by reverse phase thin layer chromatography (RP-TLC) and reverse phase high-performance liquid chromatography (RP-HPLC). In both methods, methanol was used as the organic modifier of the mobile phase. For each 2-aminothiazol-4(5H)-one derivative, a relationship was observed between the structure of the compound and the values of the lipophilicity parameters (log kw, RM0). Experimental lipophilicity values were compared with computer calculated partition coefficient (logP) values. A total of 27 of the 28 tested compounds had a lipophilicity value < 5, which therefore met the condition of Lipinski’s rule. In addition, the in silico ADME assay showed favorable absorption, distribution, metabolism, and excretion parameters for most of the pseudothiohydantoin derivatives tested. The study of lipophilicity and the ADME analysis indicate that the tested compounds are good potential drug candidates.

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“…ADME (absorption, distribution, metabolism, and excretion) studies play a vital role in drug discovery and development with the support of technology, software like SwissADME allows the prediction and compilation of ADME parameters i.e., Physiological properties, Lipophilicity, Water solubility, Pharmacokinetics, Drug likeness, Medicinal chemistry. Selective coumarins present in A.M. like umbelliferon, scopoletin, scoparone, xanthotoxol, marmesin, psoralen, imperatorin (also known as Marmelosin or marmelide), alloimperatorin, and marmin [8][9][10][11][12][13] were taken for in-silico ADME screening using SwissADME software.…”