Lipophilicity Determination of Antifungal Isoxazolo[3,4-b]pyridin-3(1H)-ones and Their N1-Substituted Derivatives with Chromatographic and Computational Methods

摘要: The lipophilicity of a molecule is well-recognized as crucial physicochemical factor that conditions the biological activity drug candidate. This study was aimed to evaluate isoxazolo[3,4-b]pyridine-3(1H)-ones and their N1-substituted derivatives, which demonstrated pronounced antifungal activities. Several methods, including reversed-phase thin layer chromatography (RP-TLC), reversed phase high-performance liquid (RP-HPLC), micellar electrokinetic (MEKC), were employed. Furthermore, calculated logP values estimated using various freely commercially available software packages online platforms, well density functional theory computations (DFT). Similarities dissimilarities between determined indices assessed several chemometric approaches. Principal component analysis (PCA) indicated other features beside affect activities investigated derivatives. Quantitative-structure-retention-relationship (QSRR) by means genetic algorithm—partial least squares (GA-PLS)—was implemented rationalize link descriptors lipophilicity. Among studied compounds, structure 16 should be considered best starting for further studies, since it lowest lipophilic character within series while retaining activity. Sum ranking differences (SRD) chromatographic approach, regardless technique employed, approach assessment isoxazolones.