Activation of the nuclear factor E2-related factor 2 pathway by novel natural products halomadurones A-D and a
Thomas P Wyche, Miranda Standiford, Yanpeng Hou
1Pharmaceutical Sciences Division, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA. tbugni@pharmacy.wisc.edu.
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.
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