In Silico Study of Chromatographic Lipophilicity Parameters of 3-(4-Substituted Benzyl)-5-Phenylhydantoins

Author(s): Tatjana Djakovic Sekulic, Svetlana Keleman, Kristina Tot, Jadranka Tot, Nemanja Trisovic, Gordana Uscumlic

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 19 , Issue 6 , 2016

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Abstract:

New synthesized compounds, particularly those with biological activity, are potential drug candidates. This article describes experimental studies performed to estimate lipophilicity parameters of new 3-(4-substituted benzyl)-5-phenylhydantoins. Lipophilicity, as one of the most important molecular characteristics for the activity, was determined using the reversed-phase liquid chromatography (RP-18 stationary phase and methanol-water mobile phase). Molecular structures were used to generate in silico data which were used to estimate pharmacokinetic properties of the investigated compounds. The results show that generally, the investigated compounds attain good bioavailability properties. A more detailed analysis shows that the presence of a nitro, methoxy and tert-butyl group in the molecule is indicated as unfavorable for the oral bioavailability of hydantoins. Multivariate exploratory analysis was used in order to visualize grouping patterns among molecular descriptors as well as among the investigated compounds. Molecular docking study performed for two hydantoins with the highest bioavailability scores shows high binding affinity to tyrosine kinase receptor IGF-1R. The results achieved can be useful as a template for future development and further derivation or modification to obtain more potent and selective antitumor agents.

Keywords: 3-(4-substituted benzyl)-5-phenylhydantoins, chromatographic lipophilicity parameters, molecular descriptors, Lipinski’s rule of five, hierarchical cluster analysis, principal component analysis, molecular docking, inhibitors of tyrosine kinases.

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Article Details

VOLUME: 19
ISSUE: 6
Year: 2016
Page: [437 - 443]
Pages: 7
DOI: 10.2174/1386207319666160506122711
Price: $65

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