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

Authors :
Koukoulitsa C
Geromichalos GD
Skaltsa H
Source :
Journal of computer-aided molecular design [J Comput Aided Mol Des] 2005 Aug; Vol. 19 (8), pp. 617-23. Date of Electronic Publication: 2005 Oct 28.
Publication Year :
2005

Abstract

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.

Details

Language :
English
ISSN :
0920-654X
Volume :
19
Issue :
8
Database :
MEDLINE
Journal :
Journal of computer-aided molecular design
Publication Type :
Academic Journal
Accession number :
16254688
Full Text :
https://doi.org/10.1007/s10822-005-9018-y