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

Abstract

Lipophilicity 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-(4substituted 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.

Chemometric study of chromatographic and computational bioactivity parameters of diphenylacetamides

“…In a plurality of molecular descriptors, the lipophilicity has a crucial role in estimating and predicting the biological activity of the compound . In addition to the partition coefficient, log P , as a standard measure of lipophilicity, the chromatographic parameters, R M 0 and m , determined by reversed‐phase thin‐layer chromatography (RPTLC) are increasingly applied as alternative criteria of lipophilicity . The reason for this is the similarity in intermolecular interactions, which determine the chromatographic and biological behavior of one molecule .…”