title: In Silico Study of Chromatographic Lipophilicity Parameters of 3-(4-Substituted Benzyl)-5-Phenylhydantoins.
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.
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Novi Sad, Republic of Serbia. tatjana.djakovic-sekulic@dh.uns.ac.rs.
authors.forename: Tatjana Djakovic
authors.initials: TD
authors.lastname: Sekulic
authors.forename: Svetlana
authors.initials: S
authors.lastname: Keleman
authors.forename: Kristina
authors.initials: K
authors.lastname: Tot
authors.forename: Jadranka
authors.initials: J
authors.lastname: Tot
authors.forename: Nemanja
authors.initials: N
authors.lastname: Trisovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Uscumlic
mesh_terms: D001682:Biological Availability; D056148:Chromatography, Reverse-Phase / Q000379:methods*; D003198:Computer Simulation; D015195:Drug Design; D006827:Hydantoins / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017526:Receptor, IGF Type 1 / Q000378:metabolism
chemical_list: D006827:Hydantoins; D008055:Lipids; C098839:5-phenylhydantoin; D017526:Receptor, IGF Type 1