VolSurf analysis of pharmacokinetic properties for several antifungal
sesquiterpene lactones isolated from Greek <Emphasis Type="Italic">Centaurea</Emphasis> sp. |
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Authors: | Email author" target="_blank">Catherine?KoukoulitsaEmail author George?D?Geromichalos Helen?Skaltsa |
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Institution: | (1) Department of Pharmacognosy & Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, GR-157 71 Athens, Greece;(2) Symeonidio Research Center, Theagenio Cancer Hospital, Thessaloniki, Greece |
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Abstract: | 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.
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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Keywords: | ADME sesquiterpene lactones virtual screening VolSurf |
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