Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation |
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| Authors: | Swarna Oli Usama Ramadan Abdelmohsen Ute Hentschel Tanja Schirmeister |
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| Institution: | 1.Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University of Mainz, Staudinger Weg 5, Mainz 55128, Germany; E-Mail: ;2.Department of Botany II, Julius-von-Sachs-Institute for Biological Sciences, University of Würzburg, Julius-von-Sachs Platz 3, Würzburg 97082, Germany; E-Mails: (U.R.A.); (U.H.);3.Department of Pharmacognosy, Faculty of Pharmacy, Minia University, Minia 61519, Egypt |
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| 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. |
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| Keywords: | Plakortis halichondroides plakortide E protease inhibitor slowly-binding reversible inhibitor cathepsin rhodesain |
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