title: VolSurf analysis of pharmacokinetic properties for several antifungal sesquiterpene lactones isolated from Greek Centaurea sp.
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.
authors.affiliation: Department of Pharmacognosy & Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, GR-157 71, Athens, Greece. koukoulitsa@pharm.uoa.gr
authors.forename: Catherine
authors.initials: C
authors.lastname: Koukoulitsa
authors.forename: George D
authors.initials: GD
authors.lastname: Geromichalos
authors.forename: Helen
authors.initials: H
authors.lastname: Skaltsa
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D031179:Centaurea / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D012995:Solubility; D013816:Thermodynamics
chemical_list: D000935:Antifungal Agents; D001798:Blood Proteins; D007783:Lactones; D012717:Sesquiterpenes