title: Correlation study of retention data and antimalarial activity of 1,2,4,5-mixed tetraoxanes with their molecular structure descriptors and LSER parameters.
abstract: The chromatographic behavior of mixed 1,2,4,5-tetraoxanes, cholic and deoxycholic acid derivatives with distinct biological activity, was examined by high-performance thin-layer chromatography in order to correlate their structure and retention. Chromatographic systems were consisted of RP-18 or CN-silica as stationary phase, and binary mixtures of water with methanol, dioxane or acetone as mobile phase. Based on the respective retentions, the lipophilicity of the investigated compounds was determined. Multiple linear regression and partial least squares have been used to select variables that best describe the behavior of the investigated compounds in chromatographic systems and to quantify influences of most important parameters. The validation and cross-validation of the QSRR model suggest its applicability for prediction and understanding of retention of congeners. The models indicate the importance of nonpolar properties of the solutes and their ability for hydrophobic interactions, as well as the importance of proton donating abilities, hydrophilic and π interactions pointing out on that way the possible separation mechanism in the studied chromatographic systems. Observed correlations between structure and biological activity of mixed 1,2,4,5-tetraoxanes, indicate that the antimalarial activity against W2 and D6 Plasmodium falciparum strains, is governed by hydrophobic feature (measured with lipophilicity parameter), hydrophilic feature (measured with HLB, %HS, HB and HBA descriptors), and electronic feature (HOMO).
authors.affiliation: Institute of Chemistry, Technology, and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia. Electronic address: sgaica@chem.bg.ac.rs.
authors.forename: Sandra
authors.initials: S
authors.lastname: Šegan
authors.affiliation: Institute of Chemistry, Technology, and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Terzić-Jovanović
authors.affiliation: Faculty of Chemistry, University of Belgrade, PO Box 51, 11158 Belgrade, Serbia.
authors.forename: Dušanka
authors.initials: D
authors.lastname: Milojković-Opsenica
authors.affiliation: Faculty of Chemistry, University of Belgrade, PO Box 51, 11158 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Trifković
authors.affiliation: Faculty of Chemistry, University of Belgrade, PO Box 51, 11158 Belgrade, Serbia.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Šolaja
authors.affiliation: Institute of Chemistry, Technology, and Metallurgy, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia. Electronic address: dopsen@chem.bg.ac.rs.
authors.forename: Dejan
authors.initials: D
authors.lastname: Opsenica
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D045568:Tetraoxanes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D045568:Tetraoxanes
keywords: Lipophilicity; Mixed 1,2,4,5-tetraoxanes; Quantitative structure activity relationship (QSAR); Quantitative structure-retention relationship (QSRR); Reversed-phase thin layer chromatography (RPTLC)