Activation of the nuclear factor E2-related factor 2 pathway by novel natural products halomadurones A-D and a synthetic analogue

Mar Drugs. 2013 Dec 16;11(12):5089-99. doi: 10.3390/md11125089.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antioxidant Response Elements / genetics
  • Bacteria / genetics
  • Bacteria / metabolism
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology*
  • Cells, Cultured
  • Halogens / metabolism
  • Mice
  • NF-E2-Related Factor 2 / genetics*
  • NF-E2-Related Factor 2 / metabolism*
  • Neurodegenerative Diseases / drug therapy
  • Pyrones / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics*

Substances

  • Biological Products
  • Halogens
  • NF-E2-Related Factor 2
  • Pyrones