Comprehensive Chemometric and Chromatographic Investigation of Lipophilicity of Biologically Active...

Background/Objectives: Previously reported analyses show that some androstane-3-oxime derivatives with picolyl and picolinylidene functional groups possess a significant anticancer activity towards various cancer cell lines. These findings suggest that these compounds have prominent biological potential and represent a good basis for further research. The present study aims to determine their anisotropic lipophilicity as a physicochemical parameter relevant to both prediction of chromatographic behavior and biological activity. Methods: Anisotropic lipophilicity was determined using reversed-phase ultra-high performance liquid chromatography (RP-UHPLC) systems equipped with three stationary phases (C18, C8 and phenyl) and three mobile phases composed of water with different modifiers (methanol, acetonitrile and a methanol-acetonitrile mixture). Capacity factors (logk) were obtained for all compounds across the chromatographic systems to describe their behavior in anisotropic environments. Chemometric analyses were performed using linear pattern recognition techniques (PRT), such as hierarchical cluster analysis (HCA) and principal component analysis (PCA), and non-linear clustering based on artificial neural networks (CANN). Results: The experimentally determined chromatographic parameters were correlated with in silico lipophilicity values (logP). This comparison allowed for examination of the concordance between experimental and computed data for the series of androstanes. The chemometric analysis resulted in models that provided an overview of the grouping of compounds in the space of the determined chromatographic parameters. Conclusions: The results demonstrate strong agreement between experimental and computational lipophilicity parameters. This very good data fit provides a reliable foundation for further studies exploring the relationships between lipophilicity and biological activity of the studied androstane derivatives.