Abstract
Extracts of the predatory myxobacterium Pyxidicoccus fallax HKI 727 showed antiproliferative effects on leukemic K-562 cells. Bioactivity-guided fractionation led to the isolation of the bis-catechol myxochelin A and two new congeners. The biosynthetic origin of myxochelins C and D was confirmed by feeding studies with isotopically labeled precursors. Pharmacological testing revealed human 5-lipoxygenase (5-LO) as a molecular target of the myxochelins. In particular, myxochelin A efficiently inhibited 5-LO activity with an IC50 of 1.9 μM and reduced the proliferation of K-562 cells at similar concentrations.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arachidonate 5-Lipoxygenase / metabolism*
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Curcumin / chemistry
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HeLa Cells
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Humans
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K562 Cells
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Lipoxygenase Inhibitors / chemistry
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Lipoxygenase Inhibitors / isolation & purification
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Lipoxygenase Inhibitors / pharmacology*
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Lysine / analogs & derivatives*
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Lysine / chemistry
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Lysine / isolation & purification
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Lysine / pharmacology
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Molecular Structure
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Myxococcales / chemistry*
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Siderophores / chemistry
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Siderophores / isolation & purification*
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Stereoisomerism
Substances
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Lipoxygenase Inhibitors
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Siderophores
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myxochelin A
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Arachidonate 5-Lipoxygenase
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Curcumin
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Lysine