title: Myxochelins target human 5-lipoxygenase.
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.
authors: Junior Research Group Secondary Metabolism of Predatory Bacteria and §Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute , Beutenbergstrasse 11a, 07745 Jena, Germany.
authors: Sebastian
authors: S
authors: Schieferdecker
authors: Stefanie
authors: S
authors: König
authors: Andreas
authors: A
authors: Koeberle
authors: Hans-Martin
authors: HM
authors: Dahse
authors: Oliver
authors: O
authors: Werz
authors: Markus
authors: M
authors: Nett
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D003474:Curcumin / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D009231:Myxococcales / Q000737:chemistry*; D017262:Siderophores / Q000737:chemistry / Q000302:isolation & purification*; D013237:Stereoisomerism
chemical_list: D016859:Lipoxygenase Inhibitors; D017262:Siderophores; C058735:myxochelin A; D001094:Arachidonate 5-Lipoxygenase; D003474:Curcumin; D008239:Lysine