title: Myxochelin-Inspired 5-Lipoxygenase Inhibitors: Synthesis and Biological Evaluation.
abstract: A total of 48 analogues of the natural product myxochelin A were prepared and evaluated for their inhibitory effects on human 5-lipoxygenase in both cell-free and cell-based assays. Structure-activity relationship analysis revealed that the secondary alcohol function and only chiral center of myxochelin A is not required for biological activity. By expanding the diaminoalkane linker of the two aromatic residues it was possible to generate a myxochelin derivative with superior activity against 5-lipoxygenase in intact cells.
authors.affiliation: Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Adolf-Reichwein-Strasse 23, 07745, Jena, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schieferdecker
authors.affiliation: Chair of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743, Jena, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: König
authors.affiliation: Chair of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743, Jena, Germany.
authors.forename: Simona
authors.initials: S
authors.lastname: Pace
authors.affiliation: Chair of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.affiliation: Department of Biochemical and Chemical Engineering, Technische Universität Dortmund, Emil-Figge-Strasse 66, 44227, Dortmund, Germany.
authors.forename: Markus
authors.identifier: 0000-0003-0847-086X
authors.initials: M
authors.lastname: Nett
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D016859:Lipoxygenase Inhibitors; C058735:myxochelin A; D001094:Arachidonate 5-Lipoxygenase; D008239:Lysine
keywords: 5-lipoxygenase; inflammation; inhibitors; leukotrienes; myxochelin