Lipophilicity Determination of Quaternary (Fluoro)Quinolones by Chromatographic and Theoretical Approaches
Abstract
:1. Introduction
2. Results and Discussion
2.1. Computationally Estimated Lipophilicity Parameters
2.2. Analysis of Chromatographic Data and Chromatographically Derived Lipophilicity Indexes
2.3. Sum of Ranking Differences of Computationally and Chromatographically Derived Lipophilicity Indexes
2.4. Quantitative Structure Retention/Activity Relationships QSRAR
3. Materials and Methods
3.1. Reagents
3.2. Analytes
3.3. TLC Analysis
3.4. MEKC Analysis
3.5. Computational Estimation of logP Values
3.6. Data Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Goetz, G.H.; Shalaeva, M. Leveraging chromatography based physicochemical properties for efficient drug design. ADMET DMPK 2018, 6, 85. [Google Scholar] [CrossRef]
- Di, L.; Kerns, E.H. Drug-Like Properties; Academic Press: New York, NY, USA, 2008. [Google Scholar]
- Godyń, J.; Hebda, M.; Więckowska, A.; Więckowski, K.; Malawska, B.; Bajda, M. Lipophilic properties of anti-Alzheimer’s agents determined by micellar electrokinetic chromatography and reversed-phase thin-layer chromatography. Electrophoresis 2017, 38, 1268–1275. [Google Scholar] [CrossRef] [PubMed]
- OECD Test Guidelines for the Chemicals. Available online: http://www.oecd.org/env/ehs/testing/oecdguidelinesforthetestingofchemicals.htm (accessed on 11 September 2019).
- Kaliszan, R. QSRR: Quantitative Structure-(Chromatographic) Retention Relationships. Chem. Rev. 2007, 107, 3212–3246. [Google Scholar] [CrossRef] [PubMed]
- Bajda, M.; Chłoń-Rzepa, G.; Żmudzki, P.; Czopek, A.; Stanisz-Wallis, K.; Łątka, K.; Pawłowski, M.; Zagórska, A. Determination of ligand efficiency indices in a group of 7H-purine-2,6-dione derivatives with psychotropic activity using micellar electrokinetic chromatography. Electrophoresis 2018, 39, 2446–2453. [Google Scholar] [CrossRef] [PubMed]
- Fedorowicz, J.; Sączewski, J.; Konopacka, A.; Waleron, K.; Lejnowski, D.; Ciura, K.; Tomašič, T.; Skok, Ž.; Savijoki, K.; Morawska, M.; et al. Synthesis and biological evaluation of hybrid quinolone-based quaternary ammonium antibacterial agents. Eur. J. Med. Chem. 2019, 179, 576–590. [Google Scholar] [CrossRef]
- Murtagh, F.; Legendre, P. Ward’s Hierarchical Agglomerative Clustering Method: Which Algorithms Implement Ward’s Criterion? J. Classif. 2014, 31, 274–295. [Google Scholar] [CrossRef]
- Kłosińska-Szmurło, E.; Pluciński, F.A.; Grudzień, M.; Betlejewska-Kielak, K.; Biernacka, J.; Mazurek, A.P. Experimental and theoretical studies on the molecular properties of ciprofloxacin, norfloxacin, pefloxacin, sparfloxacin, and gatifloxacin in determining bioavailability. J. Biol. Phys. 2014, 40, 335–345. [Google Scholar] [CrossRef] [Green Version]
- Völgyi, G.; Vizserálek, G.; Takács-Novák, K.; Avdeef, A.; Tam, K.Y. Predicting the exposure and antibacterial activity of fluoroquinolones based on physicochemical properties. Eur. J. Pharm. Sci. 2012, 47, 21–27. [Google Scholar] [CrossRef]
- Starek, M.; Komsta, Ł.; Krzek, J. Reversed-phase thin-layer chromatography technique for the comparison of the lipophilicity of selected non-steroidal anti-inflammatory drugs. J. Pharm. Biomed. Anal. 2013, 85, 132–137. [Google Scholar] [CrossRef]
- 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. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2016, 1012–1013, 144–152. [Google Scholar] [CrossRef]
- Rageh, A.H.; Atia, N.N.; Abdel-Rahman, H.M. Lipophilicity estimation of statins as a decisive physicochemical parameter for their hepato-selectivity using reversed-phase thin layer chromatography. J. Pharm. Biomed. Anal. 2017, 142, 7–14. [Google Scholar] [CrossRef] [PubMed]
- Milošević, N.P.; Dimova, V.B.; Perišić-Janjić, N.U. RP TLC data in correlation studies with in silico pharmacokinetic properties of benzimidazole and benztriazole derivatives. Eur. J. Pharm. Sci. 2013, 49, 10–17. [Google Scholar] [CrossRef] [PubMed]
- Šegan, S.; Penjišević, J.; Šukalović, V.; Andrić, D.; Milojković-Opsenica, D.; Kostić-Rajačić, S. Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2019, 1124, 146–153. [Google Scholar] [CrossRef] [PubMed]
- Hubicka, U.; Żuromska-Witek, B.; Komsta, Ł.; Krzek, J. Lipophilicity study of fifteen fluoroquinolones by reversed-phase thin-layer chromatography. Anal. Methods 2015, 7, 3841–3848. [Google Scholar] [CrossRef]
- Komsta, Ł.; Skibiński, R.; Berecka, A.; Gumieniczek, A.; Radkiewicz, B.; Radoń, M. Revisiting thin-layer chromatography as a lipophilicity determination tool—A comparative study on several techniques with a model solute set. J. Pharm. Biomed. Anal. 2010, 53, 911–918. [Google Scholar] [CrossRef]
- Sârbu, C.; Todor, S. Determination of lipophilicity of some non-steroidal anti-inflammatory agents and their relationships by using principal component analysis based on thin-layer chromatographic retention data. J. Chromatogr. A 1998, 822, 263–269. [Google Scholar] [CrossRef]
- Ciura, K.; Rutecka, A.; Szewczyk, A.; Kawczak, P.; Bączek, T.; Nowakowska, J. Study of the chromatographic behavior of selected antipsychotic drugs on RP-TLC based on quantitative structure--retention relationships. J. Iran. Chem. Soc. 2019, 16, 1019–1027. [Google Scholar] [CrossRef]
- Dąbrowska, M.; Starek, M.; Komsta, Ł.; Szafrański, P.; Stasiewicz-Urban, A.; Opoka, W. Assessment of the chromatographic lipophilicity of eight cephalosporins on different stationary phases. Eur. J. Pharm. Sci. 2017, 101, 115–124. [Google Scholar] [CrossRef]
- Šegan, S.; Božinović, N.; Opsenica, I.; Andrić, F. Consensus-based comparison of chromatographic and computationally estimated lipophilicity of benzothiepino[3,2-c]pyridine derivatives as potential antifungal drugs. J. Sep. Sci. 2017, 40, 2089–2096. [Google Scholar] [CrossRef]
- Andrić, F.; Héberger, K. Towards better understanding of lipophilicity: Assessment of in silico and chromatographic logP measures for pharmaceutically important compounds by nonparametric rankings. J. Pharm. Biomed. Anal. 2015, 115, 183–191. [Google Scholar] [CrossRef]
- Andrić, F.; Héberger, K. Chromatographic and computational assessment of lipophilicity using sum of ranking differences and generalized pair-correlation. J. Chromatogr. A 2015, 1380, 130–138. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Andrić, F.; Bajusz, D.; Rácz, A.; Šegan, S.; Héberger, K. Multivariate assessment of lipophilicity scales—computational and reversed phase thin-layer chromatographic indices. J. Pharm. Biomed. Anal. 2016, 127, 81–93. [Google Scholar] [CrossRef] [PubMed]
- Herbert, B.J.; Dorsey, J.G. n-Octanol-Water Partition Coefficient Estimation by Micellar Electrokinetic Capillary Chromatography. Anal. Chem. 1995, 67, 744–749. [Google Scholar] [CrossRef]
- Taléns-Visconti, R.; Garrigues, T.M.; Cantón, E.; Freixas, J.; Martín-Villodre, A.; Plá-Delfina, J.M. Activity–Bioavailability balance in Oral Drug Development for a Selected Group of 6-Fluoroquinolones. J. Pharm. Sci. 2002, 91, 2452–2464. [Google Scholar] [CrossRef] [PubMed]
- Tropsha, A.; Gramatica, P.; Gombar, V. The Importance of Being Earnest: Validation is the Absolute Essential for Successful Application and Interpretation of QSPR Models. QSAR Comb. Sci. 2003, 22, 69–77. [Google Scholar] [CrossRef]
- Drlica, K. Mechanism of fluoroquinolone action. Curr. Opin. Microbiol. 1999, 2, 504–508. [Google Scholar] [CrossRef]
- Asadipour, A.; Moshafi, M.H.; Khosravani, L.; Moghimi, S.; Amou, E.; Firoozpour, L.; Ilbeigi, G.; Beiki, K.; Soleimani, E.; Foroumadi, A. N-substituted piperazinyl sarafloxacin derivatives: Synthesis and in vitro antibacterial evaluation. DARU J. Pharm. Sci. 2018, 26, 199–207. [Google Scholar] [CrossRef]
- Soczewiński, E.; Wachtmeister, C.A. The relation between the composition of certain ternary two-phase solvent systems and RM values. J. Chromatogr. A 1962, 7, 311–320. [Google Scholar] [CrossRef]
- Bieganowska, M.L.; Doraczynska-Szopa, A.; Petruczynik, A. The retention behavior of some sulfonamides on different TLC plates. 2. Comparison of the selectivity of the systems and quantitative determination of hydrophobicity parameters. J. Planar Chromatogr.-Mod. TLC 1995, 8, 122–128. [Google Scholar]
Compound No. | ClogP | miLogP | KOWWINlogP | AlogPs | AClogP | AlopgP | MlogP | XlogP2 | XlogP3 | AvglogP |
---|---|---|---|---|---|---|---|---|---|---|
1 | −3.10 | −5.08 | 1.34 | 2.35 | 1.92 | 0.60 | −0.04 | 2.27 | 3.57 | 1.78 |
2 | −2.55 | −4.96 | 2.14 | 2.83 | 2.29 | 1.10 | −0.18 | 2.77 | 4.16 | 2.16 |
3 | −2.89 | −3.92 | 1.76 | 3.20 | 2.02 | 0.95 | 0.43 | 2.66 | 4.04 | 2.22 |
4 | −3.51 | −5.21 | 0.83 | 2.29 | 2.14 | 0.02 | −0.09 | 1.63 | 2.01 | 1.33 |
5 | −2.43 | −4.92 | 1.96 | 2.85 | 2.26 | 1.18 | 0.26 | 2.89 | 4.10 | 2.26 |
6 | −5.06 | −4.67 | −0.06 | 1.48 | 1.14 | −0.33 | 0.05 | 1.27 | 2.42 | 1.01 |
7 | −4.10 | −4.97 | 1.44 | 2.13 | 1.80 | 0.52 | 0.67 | 2.48 | 3.17 | 1.79 |
8 | −3.05 | −5.09 | 1.65 | 2.36 | 2.11 | 0.74 | 0.16 | 2.39 | 3.76 | 1.92 |
9 | −2.89 | −5.07 | 1.14 | 2.85 | 2.29 | 0.47 | 0.01 | 2.13 | 3.29 | 1.83 |
10 | −5.52 | −4.86 | −0.87 | 1.68 | 1.17 | −1.04 | −0.32 | 0.51 | 0.94 | 0.51 |
11 | −4.56 | −5.12 | 0.62 | 2.19 | 1.82 | −0.19 | 0.40 | 1.71 | 2.89 | 1.47 |
12 | −3.56 | −5.21 | 0.52 | 2.33 | 1.94 | −0.12 | −0.29 | 1.51 | 2.06 | 1.24 |
13 | −3.01 | −5.11 | 1.33 | 2.75 | 2.32 | 0.38 | −0.42 | 2.00 | 3.32 | 1.73 |
14 | −3.35 | −4.28 | 0.95 | 3.05 | 2.05 | 0.24 | 0.19 | 1.89 | 3.20 | 1.77 |
15 | −4.07 | −4.80 | 2.26 | 2.80 | 2.56 | 1.30 | 0.20 | 3.80 | 4.54 | 2.41 |
16 | −4.03 | −2.83 | 0.80 | 0.82 | 0.58 | 0.07 | −1.86 | 2.15 | 0.61 | 0.39 |
17 | −2.57 | −3.11 | 0.16 | 0.99 | 0.28 | −0.06 | −0.89 | 1.96 | −0.80 | 0.08 |
18 | −3.25 | −3.56 | −0.46 | 0.57 | −0.06 | −0.64 | −2.25 | 1.34 | −1.03 | −0.35 |
19 | −5.21 | −2.56 | −1.86 | −0.84 | −0.84 | −1.56 | −2.63 | 0.34 | −2.15 | −1.28 |
20 | −3.04 | −1.53 | −0.04 | 0.79 | 0.04 | −0.28 | −1.68 | 1.73 | 0.11 | 0.12 |
21 | −2.70 | −3.22 | 0.34 | 0.88 | 0.31 | −0.14 | −2.31 | 1.84 | −0.24 | 0.06 |
22 | −3.19 | −3.57 | −0.15 | 0.20 | 0.13 | −0.50 | −2.01 | 1.46 | −1.08 | −0.30 |
23 | −4.24 | −3.25 | −0.36 | 0.21 | −0.18 | −0.71 | −1.63 | 1.55 | −0.20 | −0.16 |
No. | logP Scale | Algorithms | Supplier |
---|---|---|---|
1 | ClogP | fragment contribution | www.biobyte.com (ChemDraw) |
2 | milogP | fragment contribution | www.molinspiration.com |
3 | KOWWINlogP | hybrid algorithm (atom-based approach and fragmental contribution) | www.epa.gov |
4 | AlogPs | properties dependent methods (topological descriptors) | www.vcclab.org |
5 | AClogP | atom-based method | www.acdlabs.com |
6 | AlopgP | fragment contribution | www.vcclab.org |
7 | MlogP | properties dependent methods (topological descriptors) | http://www.talete.mi.it/ |
8 | XlogP | atom-based method | http://www.compchemcons.com |
9 | XlogP3 | atom-based method | http://www.compchemcons.com |
Compound No. | RP-TLC Stationary Phase: Silica Gel C18 | RP-TLC Stationary Phase: Silica Gel C8 | MEKC | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
RM0 | b | C0 | mRM | PC1 * | RM0 | b | C0 | mRM | PC1 ** | logk | σ logk | |
1 | 1.65 | −1.36 | 1.21 | 0.96 | 0.72 | 1.99 | −1.92 | 1.04 | 1.03 | −2.23 | −0.104 | 0.0057 |
2 | 2.78 | −3.31 | 0.84 | 0.95 | 0.81 | 2.31 | −2.61 | 0.89 | 1.01 | −2.22 | −0.125 | 0.0036 |
3 | 2.75 | −3.13 | 0.88 | 1.02 | 0.34 | 2.74 | −3.17 | 0.86 | 1.15 | −3.48 | −0.070 | 0.0041 |
4 | 1.74 | −1.85 | 0.94 | 0.72 | 2.36 | 1.79 | −1.90 | 0.94 | 0.84 | −0.58 | −0.321 | 0.0117 |
5 | 2.29 | −2.45 | 0.93 | 0.94 | 0.88 | 1.90 | −1.83 | 1.04 | 0.98 | −1.69 | −0.265 | 0.0020 |
6 | 1.78 | −1.45 | 1.23 | 0.98 | 0.53 | 1.32 | −0.56 | 2.35 | 1.04 | −1.73 | −0.443 | 0.0003 |
7 | 1.87 | −1.60 | 1.17 | 0.99 | 0.48 | 1.76 | −1.43 | 1.23 | 1.05 | −2.01 | −0.239 | 0.0009 |
8 | 1.83 | −1.71 | 1.07 | 0.89 | 1.18 | 1.71 | −1.56 | 1.09 | 0.93 | −1.26 | −0.153 | 0.0007 |
9 | 1.86 | −1.91 | 0.98 | 0.81 | 1.75 | 1.62 | −1.66 | 0.97 | 0.79 | −0.11 | −0.479 | 0.0039 |
10 | 1.27 | −1.04 | 1.22 | 0.70 | 2.53 | 1.16 | −0.91 | 1.28 | 0.71 | 0.79 | −0.573 | 0.0021 |
11 | 1.72 | −1.59 | 1.08 | 0.84 | 1.51 | 1.59 | −1.50 | 1.06 | 0.84 | −0.54 | −0.398 | 0.0027 |
12 | 1.75 | −1.75 | 1.00 | 0.78 | 1.97 | 1.63 | −1.63 | 1.00 | 0.82 | −0.38 | −0.272 | 0.0012 |
13 | 2.18 | −2.47 | 0.88 | 0.82 | 1.74 | 1.82 | −1.97 | 0.92 | 0.83 | −0.64 | −0.408 | 0.0175 |
14 | 2.45 | −2.84 | 0.86 | 0.88 | 1.32 | 2.29 | −2.66 | 0.86 | 0.96 | −1.79 | −0.261 | 0.0070 |
15 | 3.56 | −4.21 | 0.84 | 1.24 | −1.12 | 2.63 | −2.88 | 0.91 | 1.19 | −3.52 | −0.250 | 0.0036 |
16 | 2.62 | −2.43 | 1.08 | 1.30 | −1.59 | 1.99 | −1.49 | 1.33 | 1.24 | −3.61 | 0.108 | 0.0001 |
17 | 2.33 | −2.03 | 1.15 | 1.22 | −1.08 | 2.06 | −1.54 | 1.34 | 1.29 | −4.09 | 0.077 | 0.0003 |
18 | 2.54 | −2.06 | 1.24 | 1.40 | −2.34 | 2.43 | −1.90 | 1.27 | 1.47 | −5.56 | 0.103 | 0.0049 |
19 | 2.39 | −1.78 | 1.35 | 1.24 | −1.24 | 1.87 | −1.13 | 1.65 | 1.30 | −3.91 | −0.170 | 0.0044 |
20 | 2.85 | −2.88 | 0.99 | 1.28 | −1.40 | 2.27 | −2.13 | 1.07 | 1.21 | −3.81 | 0.116 | 0.0005 |
21 | 2.69 | −2.55 | 1.06 | 1.31 | −1.63 | 2.68 | −2.83 | 0.95 | 1.26 | −4.29 | 0.101 | 0.0012 |
22 | 2.79 | −2.15 | 1.30 | 1.62 | −3.88 | 2.04 | −1.27 | 1.61 | 1.41 | −5.04 | 0.104 | 0.0011 |
23 | 2.70 | −1.98 | 1.37 | 1.62 | −3.86 | 2.45 | −2.00 | 1.23 | 1.45 | −5.38 | 0.156 | 0.0070 |
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Ciura, K.; Fedorowicz, J.; Andrić, F.; Greber, K.E.; Gurgielewicz, A.; Sawicki, W.; Sączewski, J. Lipophilicity Determination of Quaternary (Fluoro)Quinolones by Chromatographic and Theoretical Approaches. Int. J. Mol. Sci. 2019, 20, 5288. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215288
Ciura K, Fedorowicz J, Andrić F, Greber KE, Gurgielewicz A, Sawicki W, Sączewski J. Lipophilicity Determination of Quaternary (Fluoro)Quinolones by Chromatographic and Theoretical Approaches. International Journal of Molecular Sciences. 2019; 20(21):5288. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215288
Chicago/Turabian StyleCiura, Krzesimir, Joanna Fedorowicz, Filip Andrić, Katarzyna Ewa Greber, Alina Gurgielewicz, Wiesław Sawicki, and Jarosław Sączewski. 2019. "Lipophilicity Determination of Quaternary (Fluoro)Quinolones by Chromatographic and Theoretical Approaches" International Journal of Molecular Sciences 20, no. 21: 5288. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215288