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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiparasitic Agents / pharmacology
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Cathepsins / antagonists & inhibitors
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Cathepsins / metabolism
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Cysteine Endopeptidases / drug effects
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Dioxanes / chemistry*
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Dioxanes / pharmacology*
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Drug Screening Assays, Antitumor
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Humans
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Porifera / chemistry*
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacology*
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Trypanocidal Agents / chemistry*
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Trypanocidal Agents / pharmacology*
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Trypanosoma brucei brucei / drug effects
Substances
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Antiparasitic Agents
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Dioxanes
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Protease Inhibitors
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Trypanocidal Agents
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plakortide E
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Cathepsins
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Cysteine Endopeptidases
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rhodesain