Abstract
Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro). The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range.
Keywords:
Streptomyces axinellae; anti-trypanosomal; marine sponge; protease inhibition; tetromycin.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiprotozoal Agents / isolation & purification
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Antiprotozoal Agents / pharmacology
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Axinella / microbiology
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Cathepsin B / antagonists & inhibitors
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Cathepsin L / antagonists & inhibitors
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Coronavirus 3C Proteases
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Cysteine Endopeptidases / drug effects
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Heterocyclic Compounds, 4 or More Rings / isolation & purification*
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Heterocyclic Compounds, 4 or More Rings / pharmacology
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Leishmania major / drug effects
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Magnetic Resonance Spectroscopy
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Protease Inhibitors / isolation & purification*
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Protease Inhibitors / pharmacology
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Severe acute respiratory syndrome-related coronavirus / drug effects
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Streptomyces / chemistry
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Trypanocidal Agents / isolation & purification*
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Trypanocidal Agents / pharmacology
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Trypanosoma brucei brucei / drug effects
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Viral Proteins / antagonists & inhibitors
Substances
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Antiprotozoal Agents
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Heterocyclic Compounds, 4 or More Rings
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Protease Inhibitors
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Trypanocidal Agents
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Viral Proteins
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Cysteine Endopeptidases
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falcipain 2
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rhodesain
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Cathepsin B
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Cathepsin L
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Coronavirus 3C Proteases