Quantitative structure retention/activity relationships of biologically relevant 4-amino-7-chloroquinoline based compounds

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1012-1013; pp. 144 - 152
• Main Authors: Šegan, Sandra, Opsenica, Igor, Zlatović, Mario, Milojković-Opsenica, Dušanka, Šolaja, Bogdan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2016
• Subjects: 4‑Amino-7-chloroquinoline; Chromatography; Chromatography, Thin Layer - methods; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Lipophilicity; Mathematical models; Moisture content; Phases; Quantitative structure activity relationship (QSAR); Quantitative Structure-Activity Relationship; Quantitative structure-retention relationship (QSRR); Quinolines - analysis; Quinolines - chemistry; Reversed-phase thin-layer chromatography (RPTLC); Statistical methods; Thin layer chromatography; Three dimensional; Quantitative structure-retention relationship (QSRR); Reversed-phase thin-layer chromatography (RPTLC); Quantitative structure activity relationship (QSAR); 4‑Amino-7-chloroquinoline; Lipophilicity
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2016.01.033

•4-Amino-7-chloroquinoline based compounds with dual BoNT/A/LC and antimalarial activity were studied.•Lipophilicity was determined.•Correlations between structure, retention, and activity were performed.•Physically meaningful descriptors governing retention and activity were determined. The chromatographic behaviour of series of 4-amino-7-chloroquinoline (4,7-ACQ) based compounds was studied by reversed-phase thin-layer chromatography (RPTLC) with binary mobile phases containing water and the organic modifiers, DMSO or acetone. The lipophilicity of the studied compounds was determined by extrapolation of retention parameters RM to pure water content in mobile phase. In order to obtain some basic insight into the chromatographic behaviour and structural features of investigated compounds, PCA was performed on both chromatographic data (RM values) and calculated 2D and 3D structural descriptors. Both QSRR and QSAR models were built by means of the partial least squares (PLS) statistical method. It was found that descriptors which encode hydrophobic (dispersive) interactions have positive influence on retention, while influence of descriptors encoding polar interactions was negative. According to the obtained PLS model for inhibition of botulinum neurotoxin serotype A light chain, hydrophobic interactions influence positively on the mechanism of action of the investigated 4,7-ACQ, while polar interactions are less favoured. Contrary, the results of PLS modelling of activity against Plasmodium falciparum strains (W2, D6 and TM91C235) indicate that higher polarity of 4,7-ACQ contribute to their higher antimalarial activity.