The surge of scientific interest in the discovery of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (NRF2)-activating molecules underscores the importance of NRF2 as a therapeutic target especially for oxidative stress. The chemical reactivity and biological activities of several bioactive compounds have been linked to the presence of α,β-unsaturated structural systems. The α,β-unsaturated carbonyl, sulfonyl and sulfinyl functional groups are reportedly the major α,β-unsaturated moieties involved in the activation of the NRF2 signaling pathway. The carbonyl, sulfonyl and sulfinyl groups are generally electron-withdrawing groups, and the presence of the α,β-unsaturated structure qualifies them as suitable electrophiles for Michael addition reaction with nucleophilic thiols of cysteine residues within the proximal negative regulator of NRF2, Kelch-like ECH-associated protein 1 (KEAP1). The physicochemical property such as good lipophilicity of these moieties is also an advantage because it ensures solubility and membrane permeability required for the activation of the cytosolic NRF2/KEAP1 system. This review provides an overview of the reaction mechanism of α,β-unsaturated moiety-bearing compounds with the NRF2/KEAP1 complex, their pharmacological properties, structural activity-relationship and their effect on antioxidant and anti-inflammatory responses. As the first of its kind, this review article offers collective and comprehensive information on NRF2-activators containing α,β-unsaturated moiety with the aim of broadening their therapeutic prospects in a wide range of oxidative stress-related diseases.

An overview of NRF2-activating compounds bearing α,β-unsaturated moiety and their antioxidant effects / Chuka Egbujor, Melford; Buttari, Brigitta; Profumo, Elisabetta; Telkoparan-Akillilar, Pelin; Saso, Luciano. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:15(2022), pp. 1-37. [10.3390/ijms23158466]

An overview of NRF2-activating compounds bearing α,β-unsaturated moiety and their antioxidant effects

Brigitta Buttari;Luciano Saso
2022

Abstract

The surge of scientific interest in the discovery of Nuclear Factor Erythroid 2 (NFE2)-Related Factor 2 (NRF2)-activating molecules underscores the importance of NRF2 as a therapeutic target especially for oxidative stress. The chemical reactivity and biological activities of several bioactive compounds have been linked to the presence of α,β-unsaturated structural systems. The α,β-unsaturated carbonyl, sulfonyl and sulfinyl functional groups are reportedly the major α,β-unsaturated moieties involved in the activation of the NRF2 signaling pathway. The carbonyl, sulfonyl and sulfinyl groups are generally electron-withdrawing groups, and the presence of the α,β-unsaturated structure qualifies them as suitable electrophiles for Michael addition reaction with nucleophilic thiols of cysteine residues within the proximal negative regulator of NRF2, Kelch-like ECH-associated protein 1 (KEAP1). The physicochemical property such as good lipophilicity of these moieties is also an advantage because it ensures solubility and membrane permeability required for the activation of the cytosolic NRF2/KEAP1 system. This review provides an overview of the reaction mechanism of α,β-unsaturated moiety-bearing compounds with the NRF2/KEAP1 complex, their pharmacological properties, structural activity-relationship and their effect on antioxidant and anti-inflammatory responses. As the first of its kind, this review article offers collective and comprehensive information on NRF2-activators containing α,β-unsaturated moiety with the aim of broadening their therapeutic prospects in a wide range of oxidative stress-related diseases.
2022
KEAP1; NRF2; Parkinson’s disease; anti-inflammatory; antioxidant; carbonyl; sulfinyl; sulfonyl; α,β-unsaturated moiety; Kelch-like ECH-associated protein 1; oxidative stress; signal transduction; antioxidants; NF-E2-related factor 2
01 Pubblicazione su rivista::01g Articolo di rassegna (Review)
An overview of NRF2-activating compounds bearing α,β-unsaturated moiety and their antioxidant effects / Chuka Egbujor, Melford; Buttari, Brigitta; Profumo, Elisabetta; Telkoparan-Akillilar, Pelin; Saso, Luciano. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 23:15(2022), pp. 1-37. [10.3390/ijms23158466]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1652404
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