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Study on lipophilicity of selected uridine derivatives |
| Jadwiga Paszkowska 1, Beata Kania , Ilona Wandzik 1 |
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1. Silesian University of Technology, Department of Organic Chem., Bioorganic Chem. and Biotechnol., Krzywoustego 4, Gliwice 44-100, Poland |
| Abstract |
| In rational design of new lead compounds correlation between structural or property descriptors of compounds with their activities is of unquestionable meaning. Molecular lipophilicity is one of the most important factors in pharmaceutical research and can be considered as a key determinant of pharmacokinetic properties of a drug and its interaction with macromolecural targets. Determination of partition coefficient is of interest in medicinal chemistry since this quantitative descriptor is frequently used in quantitative structure-activity relationship (QSAR) analysis. LogP can be determined experimentally by a variety of methods or calculated by the use of appropriate software [1]. Among experimental methods RPLC techniques are widely used and replacing traditional shake-flask procedure due to their well-known advantages.
Our goal is to determine octanol-water partition coefficient of selected uridine derivatives experimentally and by means of different computational applications. This work also describes correlation between experimentally determined lipophilicity parameters and calculated logP values. Examined uridine derivatives form a broad range of compounds significantly differentiated in lipophilicity. Some highly lipophilic as well as some highly hydrophilic compounds were present in the examined set. Not for all of the substances partition coefficient can be determined by means of experimental methods because of technical reasons. The main goal is to find the most adequate computational method, that would be predictive for the studied set of uridine derivatives. Investigated compounds are presented in Figure below.
Acknowledgement Research studies part-financed by the European Union within the European Regional Development Fund (POIG. 01.01.02-14-102/09). References [1] R. Mannhold (vol. ed.) Molecular Drug Properties, Vol. 37 in: Methods and Principles in Medicinal Chemistry, R. Mannhold, H. Kubinyi, G. Folkers (eds.), Wiley-VCh Verlag: Weinheim, 2008. |
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Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Jadwiga PaszkowskaSee On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku Submitted: 2010-03-14 14:06 Revised: 2010-04-06 21:37 |
Correlations were made between two experimentally obtained parameters: logPexp (shake-flask method) and RMw (RP TLC method) and logP values calculated by nine different algorithms. There was a strong linear relationship between logPexp and RMw (r=0.96-0.99). For examined set of uridine derivatives the best correlations between RMw and calculated logP values were found for XLOGP3, ALOGPs and miLogP algorithms. All three methods represent different approach so it can be concluded that various types of computational methods can assure high predictive power for studied set of compounds.