Activation of the Nuclear Factor E2-Related Factor 2 Pathway by Novel Natural Products Halomadurones A–D and a Synthetic Analogue |
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| Authors: | Thomas P Wyche Miranda Standiford Yanpeng Hou Doug Braun Delinda A Johnson Jeffrey A Johnson Tim S Bugni |
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| Institution: | Pharmaceutical Sciences Division, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA; E-Mails: (T.P.W.); (M.S.); (Y.H.); (D.B.); (D.A.J.); (J.A.J.) |
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| 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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| Keywords: | Ecteinascidia turbinata halomadurones Actinomadura nuclear factor E2-related factor antioxidant response element |
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