Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity.

Autor:	Casares L; Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, UK., Unciti-Broceta JD; Emerald Health Biotechnology, Córdoba, Spain., Prados ME; Emerald Health Biotechnology, Córdoba, Spain., Caprioglio D; Dipartimento di Scienze Del Farmaco, Università Del Piemonte Orientale, Novara, Italy., Mattoteia D; Dipartimento di Scienze Del Farmaco, Università Del Piemonte Orientale, Novara, Italy., Higgins M; Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, UK., Apendino G; Dipartimento di Scienze Del Farmaco, Università Del Piemonte Orientale, Novara, Italy., Dinkova-Kostova AT; Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, UK., Muñoz E; Instituto Maimónides de Investigación Biomédica de Córdoba, Spain; Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Spain; Hospital Universitario Reina Sofía, Córdoba, Spain., de la Vega L; Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, UK. Electronic address: l.delavega@dundee.ac.uk.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2020 Oct; Vol. 37, pp. 101689. Date of Electronic Publication: 2020 Aug 22.
DOI:	10.1016/j.redox.2020.101689
Abstrakt:	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. (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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