6533b7cefe1ef96bd1257137
RESEARCH PRODUCT
Identification of Plakortide E from the Caribbean Sponge Plakortis halichondroides as a Trypanocidal Protease Inhibitor using Bioactivity-Guided Fractionation
Swarna OliUsama Ramadan AbdelmohsenUte HentschelTanja Schirmeistersubject
ProteasesStereochemistrymedicine.medical_treatmentTrypanosoma brucei bruceiPlakortis halichondroidesPharmaceutical ScienceTrypanosoma brucei01 natural sciences570 Life sciencesDioxanesprotease inhibitor03 medical and health sciencesddc:593Drug DiscoverymedicineAnimalsHumansProtease Inhibitorscathepsinlcsh:QH301-705.5Pharmacology Toxicology and Pharmaceutics (miscellaneous)IC50030304 developmental biologyTrypanocidal agentrhodesainchemistry.chemical_classification0303 health sciencesProteaseAntiparasitic Agentsbiology010405 organic chemistryCommunicationplakortide Ebiology.organism_classificationCathepsinsTrypanocidal AgentsAntiparasitic agentProtease inhibitor (biology)Porifera0104 chemical sciencesCysteine Endopeptidasesslowly-binding reversible inhibitorEnzymelcsh:Biology (General)BiochemistrychemistryDrug Screening Assays Antitumor570 Biowissenschaftenmedicine.drugdescription
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 mu M and without cytotoxic effects against J774.1 macrophages at 100 mu M 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-05-01 |