Integral Lipophilicity Studies with in Silico ADMET Parameter Analysis of Novel Pseudothiohydantoin Derivatives

This article describes the assessment of the lipophilicity of 18 new pseudothiohydantoin (2-aminothiazol-4(5H)-one) derivatives using experimental and computational methods. Previous studies have shown that the tested derivatives are inhibitors of 11β-hydroxysteroid dehydrogenase type 1 and inhibit the metabolic activity of selected cancer cell lines. Lipophilicity, as log k_w and R_M0, was determined using reversed-phase high-performance liquid chromatography (RP-HPLC) and reversed-phase thin-layer chromatography (RP-TLC), respectively. In both chromatographic methods, methanol served as a modifier of the mobile phase. The obtained R_M0 values were higher than the log k_w for most of the compounds analyzed. The chromatographically determined lipophilicity parameters were compared with those obtained using the commonly used VCCLAB software: milogP, AlogPs, AClogP, XLOGP2, and XLOGP3. Among the analyzed calculation methods, the best agreement with experimentally determined lipophilicity (both log k_w and R_M0) was demonstrated by milogP and AClogP values. All tested derivatives satisfied the Lipinski, Veber, Ghose, and Egan rules, indicating their favorable properties after oral administration. Additionally, in silico calculations of ADMET parameters revealed that most of the 18 compounds tested exhibited promising pharmacokinetic and toxicological properties, making them attractive drug candidates.