A comparative study of chromatographic lipophilicity and bioactivity parameters of selected spirohydantoins
Kristina Tot, Anita Lazić, Tatjana Djaković‐Sekulić · Journal of Liquid Chromatography & Related Technologies · 2020
In this study, lipophilicity of 21 cycloalkylspiro-5-hidantoins was assessed. The overall goal of lipophilicity evaluation is preliminary investigation which should result in a decrease of the traditionally high attrition rates for compounds entering clinical trials. Lipophilicity assessment was done by reversed-phase thin-layer chromatography and in silico methods. Chromatographic analyses were performed on C-18 modified thin-layer of silica gel with a two-component mobile phase consisting of water and organic solvent (acetonitrile, acetone, dioxane, or tetrahydrofuran) in different ratios. The chromatographic lipophilicities (RM0) were discussed and compared with computational log Ps calculated with various algorithms as well as in silico ADMET descriptors using linear regression and multivariate approach (hierarchical cluster analysis and principal component analysis). A high correlation was obtained between RM0 values and calculated log P indicating a strong relationship between the variables. Multivariate data analysis enabled the comparison of the chemical structures, lipophilicity, pharmacokinetic predictors and toxicity of the investigated compounds.