Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy

Nicole Lounsbury, George Mateo, Brielle Jones, Srinivas Papaiahgari, Rajash K. Thimmulappa, Christiana Teijaro, John Gordon, Kenneth Korzekwa, Min Ye, Graham Allaway, Magid Abou-Gharbia, Shyam Biswal, Wayne Childers

Research output: Contribution to journalArticle

Abstract

Nrf2 activators represent a good drug target for designing agents to treat diseases associated with oxidative stress. Building upon previous work, we designed and prepared a series of heterocyclic chalcone-based Nrf2 activators with reduced lipophilicity and, in some cases, greater in vitro potency compared to the respective carbocyclic scaffold. These changes resulted in enhanced oral bioavailability and a superior pharmacodynamic effect in vivo.

Original languageEnglish (US)
Pages (from-to)5352-5359
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume23
Issue number17
DOIs
StatePublished - Sep 1 2015

Keywords

  • Bioavailability
  • Chalcone
  • Keap1
  • Nrf2
  • Solubility

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Lounsbury, N., Mateo, G., Jones, B., Papaiahgari, S., Thimmulappa, R. K., Teijaro, C., Gordon, J., Korzekwa, K., Ye, M., Allaway, G., Abou-Gharbia, M., Biswal, S., & Childers, W. (2015). Heterocyclic chalcone activators of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with improved in vivo efficacy. Bioorganic and Medicinal Chemistry, 23(17), 5352-5359. https://doi.org/10.1016/j.bmc.2015.07.056