title: Activation of the nuclear factor E2-related factor 2 pathway by novel natural products halomadurones A-D and a synthetic analogue.
abstract: Two novel chlorinated pyrones, halomadurones A and B, and two novel brominated analogues, halomadurones C and D, were isolated from a marine Actinomadura sp. cultivated from the ascidian Ecteinascidia turbinata. Additionally, a non-halogenated analogue, 2-methyl-6-((E)-3-methyl-1,3-hexadiene)-γ-pyrone, was synthesized to understand the role of the halogens for activity. Halomadurones C and D demonstrated potent nuclear factor E2-related factor antioxidant response element (Nrf2-ARE) activation, which is an important therapeutic approach for treatment of neurodegenerative diseases.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Wyche
authors.forename: Miranda
authors.initials: M
authors.lastname: Standiford
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: Hou
authors.forename: Doug
authors.initials: D
authors.lastname: Braun
authors.forename: Delinda A
authors.initials: DA
authors.lastname: Johnson
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
authors.affiliation: Pharmaceutical Sciences Division, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA. tbugni@pharmacy.wisc.edu.
authors.forename: Tim S
authors.initials: TS
authors.lastname: Bugni
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements / Q000235:genetics; D001419:Bacteria / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000302:isolation & purification* / Q000494:pharmacology*; D002478:Cells, Cultured; D006219:Halogens / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D011753:Pyrones / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*
chemical_list: D001688:Biological Products; D006219:Halogens; D051267:NF-E2-Related Factor 2; D011753:Pyrones