Abstract
In the course of a screening for compounds inhibiting the growth of two human breast cancer cells lines, two highly cytotoxic compounds were isolated from fermentations of Myrothecium roridum. The elucidation of their structures revealed that they are macrocyclic trichothecenes of the verrucarin type, 16-hydroxyverrucarin A (1), reported here as a natural product for the first time, and verrucarin X (2), a new compound. Both 1 and 2 exhibit moderate antifungal activity and pronounced cytotoxic activity, with IC50 values in the nanomolar (1) and micromolar (2) range. Both compounds preferentially inhibit in vivo protein biosynthesis.
MeSH terms
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Adenocarcinoma
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Ascomycota*
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Cell Line, Tumor
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Cell Survival / drug effects
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Colonic Neoplasms
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HL-60 Cells
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Humans
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Jurkat Cells
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Macrolides / chemistry*
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Macrolides / isolation & purification*
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Macrolides / pharmacology
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Conformation
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Protein Synthesis Inhibitors / chemistry
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Protein Synthesis Inhibitors / isolation & purification*
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Protein Synthesis Inhibitors / pharmacology
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Trichothecenes / chemistry
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Trichothecenes / isolation & purification*
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Trichothecenes / pharmacology
Substances
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Macrolides
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Protein Synthesis Inhibitors
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Trichothecenes
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verrucarin X
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16-hydroxyverrucarin A
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muconomycin A