Quantitative structure retention/activity relationships of biologically relevant 4-amino-7-chloroquinoline based compounds
Abstract
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 R-M 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 (R-M 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.
Keywords:
4-Amino-7-chloroquinoline / Reversed-phase thin-layer chromatography (RPTLC) / Lipophilicity / Quantitative structure-retention relationship (QSRR) / Quantitative structure activity relationship (QSAR)Source:
Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2016, 1012, 144-152Publisher:
- Elsevier
Funding / projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
DOI: 10.1016/j.jchromb.2016.01.033
ISSN: 1570-0232
PubMed: 26827282
WoS: 000370882800020
Scopus: 2-s2.0-84955618060
Collections
Institution/Community
IHTMTY - JOUR AU - Šegan, Sandra AU - Opsenica, Igor AU - Zlatović, Mario AU - Milojković-Opsenica, Dušanka AU - Šolaja, Bogdan PY - 2016 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1960 AB - 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 R-M 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 (R-M 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. PB - Elsevier T2 - Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences T1 - Quantitative structure retention/activity relationships of biologically relevant 4-amino-7-chloroquinoline based compounds VL - 1012 SP - 144 EP - 152 DO - 10.1016/j.jchromb.2016.01.033 ER -
@article{ author = "Šegan, Sandra and Opsenica, Igor and Zlatović, Mario and Milojković-Opsenica, Dušanka and Šolaja, Bogdan", year = "2016", abstract = "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 R-M 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 (R-M 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.", publisher = "Elsevier", journal = "Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences", title = "Quantitative structure retention/activity relationships of biologically relevant 4-amino-7-chloroquinoline based compounds", volume = "1012", pages = "144-152", doi = "10.1016/j.jchromb.2016.01.033" }
Šegan, S., Opsenica, I., Zlatović, M., Milojković-Opsenica, D.,& Šolaja, B.. (2016). Quantitative structure retention/activity relationships of biologically relevant 4-amino-7-chloroquinoline based compounds. in Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences Elsevier., 1012, 144-152. https://doi.org/10.1016/j.jchromb.2016.01.033
Šegan S, Opsenica I, Zlatović M, Milojković-Opsenica D, Šolaja B. Quantitative structure retention/activity relationships of biologically relevant 4-amino-7-chloroquinoline based compounds. in Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences. 2016;1012:144-152. doi:10.1016/j.jchromb.2016.01.033 .
Šegan, Sandra, Opsenica, Igor, Zlatović, Mario, Milojković-Opsenica, Dušanka, Šolaja, Bogdan, "Quantitative structure retention/activity relationships of biologically relevant 4-amino-7-chloroquinoline based compounds" in Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 1012 (2016):144-152, https://doi.org/10.1016/j.jchromb.2016.01.033 . .