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VolSurf analysis of pharmacokinetic properties for several antifungal sesquiterpene lactones isolated from Greek Centaurea sp.

Journal of Computer-Aided Molecular Design volume 19, pages 617–623 (2005)Cite this article

Summary

Sesquiterpene lactones are terpenoid compounds characteristic of the Asteraceae (Compositae) possessing a variety of biological activities, such as cytotoxic, antitumor, antibacterial, and antifungal. The prediction of the pharmacokinetic profile of several antifungal sesquiterpene lactones, isolated from Greek taxa of Centaurea sp., was undertaken in this study using the VolSurf procedure. The molecules were projected on the following pre-calculated ADME models: Caco-2 cell permeability, plasma protein affinity, blood–brain barrier permeation and thermodynamic solubility. The in silico projection revealed a non optimal pharmacokinetic profile for the studied compounds. ADME in silico screening of a semi-synthetic derivatives virtual library has been performed in order to optimize the pharmacokinetic properties. A number of derivatives were proposed as it was predicted to have higher Caco-2 cell permeability, while the pharmacokinetic behaviour regarding BBB penetration, protein binding and solubility was mainly preserved.

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Abbreviations

ADME:

absorption, distribution, metabolism, excretion

BBB:

blood brain barrier

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Acknowledgements

We are grateful to Prof. Gabriele Cruciani (Laboratory for Chemometrics, School of Chemistry, University of Perugia, Italy) for providing us the VolSurf program (version 4, Linux, www.moldiscovery.com), and also to Dr. Emanuele Carosati and Dr. Giovanni Cianchetta (same laboratory) for helpful advises. This research was financially supported by the Italian Ministry of Education.

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Authors and Affiliations

  1. Department of Pharmacognosy & Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, GR-157 71, Athens, Greece

    Catherine Koukoulitsa & Helen Skaltsa

  2. Symeonidio Research Center, Theagenio Cancer Hospital, Thessaloniki, Greece

    George D. Geromichalos

Authors
  1. Catherine Koukoulitsa
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  2. George D. Geromichalos
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  3. Helen Skaltsa
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Corresponding author

Correspondence to Catherine Koukoulitsa.

Additional information

Part of the results has been presented in: [36] 11th Panhellenic Pharmaceutical Congress [37] 15th European Symposium on Quantitative Structure-Activity Relationships & Molecular Modelling

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Koukoulitsa, C., Geromichalos, G.D. & Skaltsa, H. VolSurf analysis of pharmacokinetic properties for several antifungal sesquiterpene lactones isolated from Greek Centaurea sp.. J Comput Aided Mol Des 19, 617–623 (2005). https://doi.org/10.1007/s10822-005-9018-y

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  • DOI: https://doi.org/10.1007/s10822-005-9018-y

Keywords

  • ADME, sesquiterpene lactones, virtual screening, VolSurf