Abstract
Lipophilicity is a vital physicochemical parameter of a molecule, which affects several biological processes such as absorption, tissue distribution, and pharmacokinetic properties. In this study, evaluation of lipophilicities of a series of novel fluoroquinolone-Safirinium dye hybrids using chromatographic and computational methods is presented. Fluoroquinolone-Safirinium dye hybrids have been synthesized as new dual-acting hydrophilic antibacterial agents. Reversed phase thin-layer chromatography and micellar electrokinetic chromatography experiments were carried out. Furthermore, logP values of the target structures were predicted by means of different software platforms and algorithms. In order to assess similarities and dissimilarities of the obtained lipophilicity indexes, cluster analysis and sum of ranking differences were performed. The significant differences of calculated logP values (α = 0.05, p < 0.001) indicated that an experimental approach is necessary for lipophilicity prediction of this class of antibiotics. Chromatographic data indicated that the newly synthesized hybrid (fluoro)quinolone-based quaternary ammonium derivatives show less lipophilic character than the parent (fluoro)quinolones. Additionally, the chromatographically obtained lipophilicity indexes were evaluated for possible application in quantitative retention–activity relationships. The established lipophilicity models have the potential to predict antimicrobial activities of a series of quaternary (fluoro)quinolones against Bacillus subtilis, Escherichia coli, and Proteus vulgaris.
Highlights
Lipophilicity is one of the most frequently examined physicochemical properties of drug candidates
The main goal of this study was to evaluate the lipophilicities of a series of fluoroquinoloneSafirinium dye hybrids and their parent fluoroquinolones using typical reversed phase thin layer chromatography (RP-TLC) approach, micellar electrokinetic chromatography (MEKC), and computational methods
Vast differences between calculated logP parameters indicated that experimental procedures are still required for lipophilicity determination of this chemical group
Summary
Lipophilicity is one of the most frequently examined physicochemical properties of drug candidates. It is determined in order to support quantitative structure-activity relationships (QSAR), including prediction of biological process such as absorption, tissue distribution, and others pharmacokinetic properties [1,2]. Lipophilicity is characterized by solute distribution in biphasic liquid-liquid or solid-liquid systems. The traditional method proposed by Hansch and co-workers involves a shake-flask procedure where partition coefficient of the target compound between n-octanol and water (logP) is assessed. This method is practically not applied nowadays, the logP universal scale is generally used to represent lipophilic character of a molecule [4]
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