Chromatographic and in silico assessment of logP measures for new spirohydantoin derivatives with anticancer activity

Abstract

AbstractLipophilicity has, for a long time, been recognized as a meaningful parameter in structure‐activity relationships. It is also the single most informative physicochemical property that reveals a wealth of information on intermolecular forces, intramolecular interactions, and molecular structure in the broadest sense. In this paper, a total of 14 chromatographic measures of lipophilicity (thin‐layer chromatography and high‐performance liquid chromatography) and 11 computationally estimated logP‐s for 21 newly synthesized 3‐(4‐substituted benzyl)‐cycloalkylspiro‐5‐hidantoin derivatives have been investigated. Similarities among the investigated compounds as well as lipophilicity measures were examined by the multivariate exploratory analysis, principal component analysis, hierarchical cluster analysis, and sum of ranking differences. These chemometric approaches reveal the arrangement of investigated compounds into clusters according to lipophilicity. Chemometric consideration of lipophilicity renders principal component scores as entirely unsuitable lipophilicity measures. Furthermore, the logP values estimated from calibration graph by using a set of standard reference compounds were equivalent to the corresponding chromatographic descriptors of hydantoins extrapolated from linear relationship between retention parameters and mobile phase composition. Comparison of the 2 chromatographic techniques places high‐performance liquid chromatography lipophilicity indices slightly ahead of thin‐layer chromatography.