title: Phloroglucinol derivatives from Hypericum empetrifolium with antiproliferative activity on endothelial cells.
abstract: Five acylphloroglucinols substituted with monoterpenoids (empetrifelixin A-D and empetrikajaforin), three known monocyclic acylphloroglucinols and one monocyclic acylphloroglucinol were isolated from a petrol ether extract of Hypericum empetrifolium after fractionation by flash chromatography on silica gel, RP-18 and subsequent purification by preparative HPLC (RP-18). Their structures were elucidated by 1D, 2D NMR techniques and HREIMS. To determine a possible anti-angiogenic activity, inhibition of cell proliferation was measured using a human microvascular endothelial cell line (HMEC-1). Subconfluent grown HMEC-1 cells were treated with all compounds isolated in sufficient amounts and stained with crystal violet. Highest activity was observed for empetrifelixin A and empetrifelixin D showing a concentration dependent inhibition of cell proliferation with IC(50) values of 6.5 ± 0.1 and 7.3 ± 0.4 μM, respectively. Empetrifelixin A also showed activity in a cell migration assay with HMEC-1 cells in low micromolar concentrations.
authors.affiliation: Universität Regensburg, Pharmaceutical Biology, Universitätsstr. 31, D-93053 Regensburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schmidt
authors.forename: Guido
authors.initials: G
authors.lastname: Jürgenliemk
authors.forename: Helen
authors.initials: H
authors.lastname: Skaltsa
authors.forename: Jörg
authors.initials: J
authors.lastname: Heilmann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D010696:Phloroglucinol