title: Identification of plakortide E from the Caribbean sponge Plakortis halichondroides as a trypanocidal protease inhibitor using bioactivity-guided fractionation.
abstract: In this paper, we report new protease inhibitory activity of plakortide E towards cathepsins and cathepsin-like parasitic proteases. We further report on its anti-parasitic activity against Trypanosoma brucei with an IC₅₀ value of 5 μM and without cytotoxic effects against J774.1 macrophages at 100 μM concentration. Plakortide E was isolated from the sponge Plakortis halichondroides using enzyme assay-guided fractionation and identified by NMR spectroscopy and mass spectrometry. Furthermore, enzyme kinetic studies confirmed plakortide E as a non-competitive, slowly-binding, reversible inhibitor of rhodesain.
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University of Mainz, Staudinger Weg 5, Mainz 55128, Germany. swarnoli@uni-mainz.de.
authors.forename: Swarna
authors.initials: S
authors.lastname: Oli
authors.affiliation: Department of Botany II, Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs Platz 3, Würzburg 97082, Germany. usama.ramadan@uni-wuerzburg.de.
authors.forename: Usama Ramadan
authors.initials: UR
authors.lastname: Abdelmohsen
authors.affiliation: Department of Botany II, Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs Platz 3, Würzburg 97082, Germany. ute.hentschel@uni-wuerzburg.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Hentschel
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University of Mainz, Staudinger Weg 5, Mainz 55128, Germany. schirmei@uni-mainz.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000187:drug effects; D004146:Dioxanes / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011161:Porifera / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects
chemical_list: D000977:Antiparasitic Agents; D004146:Dioxanes; D011480:Protease Inhibitors; D014344:Trypanocidal Agents; C000593620:plakortide E; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C446033:rhodesain