Towards better understanding of lipophilicity: Assessment of in silico and chromatographic logP measures for pharmaceutically important compounds by nonparametric rankings
Abstract
Lipophilicity is one of the most frequently used physicochemical properties that affects compound solubility, determines its passive transport through biological membranes, influences biodistribution, metabolism and pharmacokinetics. We compared, ranked and grouped chromatographic lipophilicity indices and computationally estimated logP-s by sensitive and robust non-parametric approaches: sum of ranking differences (SRD) and generalized pairwise correlation method (GPCM). Chromatographic indices of fourteen neurotoxins and twenty one 1,2,4-triazole compounds have been derived from typical reversed-phase thin-layer chromatography and micellar chromatography. They were compared with in silico estimated logP-s. Under typical reversed-phase conditions, octadecyl-, octyl-, and cyanopropyl-modified silica have clear advantage over ethyl-, aminopropyl, and diol-modified beds, i.e., the preferable choice of the stationary phase follows this order: octadecyl gt octyl gt cyanopropyl gt eth...yl gt octadecyl wettable gt aminopropyl gt diol. Many of these indices outperform the majority of computationally estimated logP-s. Clear distinction can be made based on cross-validation and statistical tests. Oppositely, micellar chromatography may not be successfully used for the lipophilicity assessment, since retention parameters obtained from the typical reversed-phase conditions outperform the parameters obtained by micellar chromatography. Both ranking approaches, SRD and GPCM, although based on different background, provide highly similar variable ordering and grouping leading to the same, above mentioned conclusions. However, GPCM results in more degeneracy, i.e., in some cases it cannot distinguish the lipophilicity parameters whereas SRD and its cross-validated version can. On the other hand GPCM produces a more characteristic grouping. Both methods can be successfully used for selection of the most and least appropriate lipophilicity measures.
Keywords:
Lipophilicity / Natural toxins / Antifungal drugs / Thin-layer chromatography / Sum of ranking differences / Generalized pairwise-correlation method / Multivariate data analysisSource:
Journal of Pharmaceutical and Biomedical Analysis, 2015, 115, 183-191Publisher:
- Elsevier Science Bv, Amsterdam
Funding / projects:
- Structure-properties relationships of natural and synthetic molecules and their metal complexes (RS-MESTD-Basic Research (BR or ON)-172017)
- OTKA (Hungary) [K112547]
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3456
DOI: 10.1016/j.jpba.2015.07.006
ISSN: 0731-7085
PubMed: 26218287
WoS: 000363439500023
Scopus: 2-s2.0-84937944366
Collections
Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Andrić, Filip AU - Héberger, Karoly PY - 2015 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1987 AB - Lipophilicity is one of the most frequently used physicochemical properties that affects compound solubility, determines its passive transport through biological membranes, influences biodistribution, metabolism and pharmacokinetics. We compared, ranked and grouped chromatographic lipophilicity indices and computationally estimated logP-s by sensitive and robust non-parametric approaches: sum of ranking differences (SRD) and generalized pairwise correlation method (GPCM). Chromatographic indices of fourteen neurotoxins and twenty one 1,2,4-triazole compounds have been derived from typical reversed-phase thin-layer chromatography and micellar chromatography. They were compared with in silico estimated logP-s. Under typical reversed-phase conditions, octadecyl-, octyl-, and cyanopropyl-modified silica have clear advantage over ethyl-, aminopropyl, and diol-modified beds, i.e., the preferable choice of the stationary phase follows this order: octadecyl gt octyl gt cyanopropyl gt ethyl gt octadecyl wettable gt aminopropyl gt diol. Many of these indices outperform the majority of computationally estimated logP-s. Clear distinction can be made based on cross-validation and statistical tests. Oppositely, micellar chromatography may not be successfully used for the lipophilicity assessment, since retention parameters obtained from the typical reversed-phase conditions outperform the parameters obtained by micellar chromatography. Both ranking approaches, SRD and GPCM, although based on different background, provide highly similar variable ordering and grouping leading to the same, above mentioned conclusions. However, GPCM results in more degeneracy, i.e., in some cases it cannot distinguish the lipophilicity parameters whereas SRD and its cross-validated version can. On the other hand GPCM produces a more characteristic grouping. Both methods can be successfully used for selection of the most and least appropriate lipophilicity measures. PB - Elsevier Science Bv, Amsterdam T2 - Journal of Pharmaceutical and Biomedical Analysis T1 - Towards better understanding of lipophilicity: Assessment of in silico and chromatographic logP measures for pharmaceutically important compounds by nonparametric rankings VL - 115 SP - 183 EP - 191 DO - 10.1016/j.jpba.2015.07.006 ER -
@article{ author = "Andrić, Filip and Héberger, Karoly", year = "2015", abstract = "Lipophilicity is one of the most frequently used physicochemical properties that affects compound solubility, determines its passive transport through biological membranes, influences biodistribution, metabolism and pharmacokinetics. We compared, ranked and grouped chromatographic lipophilicity indices and computationally estimated logP-s by sensitive and robust non-parametric approaches: sum of ranking differences (SRD) and generalized pairwise correlation method (GPCM). Chromatographic indices of fourteen neurotoxins and twenty one 1,2,4-triazole compounds have been derived from typical reversed-phase thin-layer chromatography and micellar chromatography. They were compared with in silico estimated logP-s. Under typical reversed-phase conditions, octadecyl-, octyl-, and cyanopropyl-modified silica have clear advantage over ethyl-, aminopropyl, and diol-modified beds, i.e., the preferable choice of the stationary phase follows this order: octadecyl gt octyl gt cyanopropyl gt ethyl gt octadecyl wettable gt aminopropyl gt diol. Many of these indices outperform the majority of computationally estimated logP-s. Clear distinction can be made based on cross-validation and statistical tests. Oppositely, micellar chromatography may not be successfully used for the lipophilicity assessment, since retention parameters obtained from the typical reversed-phase conditions outperform the parameters obtained by micellar chromatography. Both ranking approaches, SRD and GPCM, although based on different background, provide highly similar variable ordering and grouping leading to the same, above mentioned conclusions. However, GPCM results in more degeneracy, i.e., in some cases it cannot distinguish the lipophilicity parameters whereas SRD and its cross-validated version can. On the other hand GPCM produces a more characteristic grouping. Both methods can be successfully used for selection of the most and least appropriate lipophilicity measures.", publisher = "Elsevier Science Bv, Amsterdam", journal = "Journal of Pharmaceutical and Biomedical Analysis", title = "Towards better understanding of lipophilicity: Assessment of in silico and chromatographic logP measures for pharmaceutically important compounds by nonparametric rankings", volume = "115", pages = "183-191", doi = "10.1016/j.jpba.2015.07.006" }
Andrić, F.,& Héberger, K.. (2015). Towards better understanding of lipophilicity: Assessment of in silico and chromatographic logP measures for pharmaceutically important compounds by nonparametric rankings. in Journal of Pharmaceutical and Biomedical Analysis Elsevier Science Bv, Amsterdam., 115, 183-191. https://doi.org/10.1016/j.jpba.2015.07.006
Andrić F, Héberger K. Towards better understanding of lipophilicity: Assessment of in silico and chromatographic logP measures for pharmaceutically important compounds by nonparametric rankings. in Journal of Pharmaceutical and Biomedical Analysis. 2015;115:183-191. doi:10.1016/j.jpba.2015.07.006 .
Andrić, Filip, Héberger, Karoly, "Towards better understanding of lipophilicity: Assessment of in silico and chromatographic logP measures for pharmaceutically important compounds by nonparametric rankings" in Journal of Pharmaceutical and Biomedical Analysis, 115 (2015):183-191, https://doi.org/10.1016/j.jpba.2015.07.006 . .