Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

Laura Casares Perez, Juan Diego Unciti-Broceta, Maria Eugenia Prados, Diego Caprioglio, Daiana Mattoteia, Maureen Higgins, Giovanni Apendino, Albena T. Dinkova-Kostova, Eduardo Muñoz, Laureano de la Vega (Lead / Corresponding author)

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Abstract

Oxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.
Original languageEnglish
Article number101689
Pages (from-to)1-10
Number of pages10
JournalRedox Biology
Volume37
Early online date22 Aug 2020
DOIs
Publication statusPublished - Oct 2020

Keywords

  • Cannabidiol derivative
  • NRF2
  • BACH1
  • HMOX1
  • Neurodegenerative diseases
  • Cannabidiol derivative/ NRF2/ BACH1/ HMOX1/ neurodegenerative diseases

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