title: In vitro structure-toxicity relationship of chalcones in human hepatic stellate cells.
abstract: Xanthohumol (XN), the major prenylated chalcone from hops (Humulus lupulus L.), has received much attention within the last years, due to its multiple pharmacological activities including anti-proliferative, anti-inflammatory, antioxidant, pro-apoptotic, anti-bacterial and anti-adhesive effects. However, there exists a huge number of metabolites and structurally-related chalcones, which can be expected, or are already known, to exhibit various effects on cells. We have therefore analyzed the effects of XN and 18 other chalcones in a panel, consisting of multiple cell-based assays. Readouts of these assays addressed distinct aspects of cell-toxicity, like proliferation, mitochondrial health, cell cycle and other cellular features. Besides known active structural elements of chalcones, like the Michael system, we have identified several moieties that seem to have an impact on specific effects and toxicity in human liver cells in vitro. Based on these observations, we present a structure-toxicity model, which will be crucial to understand the molecular mechanisms of wanted effects and unwanted side-effects of chalcones.
authors.affiliation: Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Zenger
authors.affiliation: CEMSE Division, King Abdullah University of Science and Technology, Saudi Arabia.
authors.forename: Subhajit
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Carl Zeiss Microscopy GmbH, Göttingen, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Wolff
authors.affiliation: CEMSE Division, King Abdullah University of Science and Technology, Saudi Arabia.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Genton
authors.affiliation: Pharmaceutical Biology, Institute of Pharmacy, University of Regensburg, Regensburg, Germany. Electronic address: birgit1.kraus@chemie.uni-regensburg.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Kraus
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000633:toxicity*; D005419:Flavonoids / Q000633:toxicity; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D006801:Humans; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000187:drug effects; D011427:Propiophenones / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D005419:Flavonoids; D011427:Propiophenones; C104536:xanthohumol
keywords: Chalcones; Hepatic stellate cell; Structure activity relationship; Xanthohumol