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.

Natural Products from Plants and Fungi as Fungicides

“…They display a wide spectrum of biological activity, one of the most important of which is antifungal activity. The general mechanism of action is considered to be alkylation of biological nucleophiles such as cysteine (cys) and glutathione or sulfhydryl-containing systems, phosphofructoki-nase and glycogen synthetase by a,b-unsaturated carbonyl structures in a Michael-type addition (Koukoulitsa et al, 2005). This group of compounds was analyzed for potential antifungal activity, in vitro against Aspergillus niger, A. ochraceus, Penicillium ochrochloron, Trichoderma viride, Fusarium tricinctum, Phomopsis helianthi and Cladosporium cladosporioides.…”

How to Extend the Use of Grid‐Based Interaction Energy Maps from Chemistry to Biotopics

“…The choice of this application was intentional; we select a product that is solid from a theoretical point of view and well known to most medicinal chemists, even more so now because of work recently done by Molecular Discover as discussed below. It was also selected for its application in describing surface protein [16][17][18] and pharmacokinetic [19][20][21] properties. GRID was designed for investigating macromolecules and their interactions with small ligands, and takes into account all major pitfalls of this type of product, [22] namely the sophisticated treatment of electrostatics, ionization, conformational flexibility and the presence of water molecules in the proteinligand interaction.…”

Antimicrobial property and antiproliferative activity of Centaurea babylonica (L.) L. on human carcinomas and cervical cancer cell lines

“…In traditional medicine, they are used for fever, menstrual disorders, vaginal candidiasis, the treatment of liver, kidney and ulcer diseases, as antidiarrheal, stomachic, tonic, appetitive, antidiabetic, antipyretic, as well as a diuretic and expectorant [10]. The genus Centaurea L. has also been the subject of many antimicrobial and antioxidant activity studies [11][12][13][14][15][16][17][18][19][20][21], antifungal [22,23], anti-colon cancer [24] and cytotoxic activities [24,25]. Additionally, the flower heads of C. cyanus are commonly used in European traditional medicine for the treatment of minor ocular inflammation, and in vivo anti-inflammatory and immunological activities of C. cyanus have been reported [26].…”