| Title: |
An overview of NRF2-activating compounds bearing α,β-unsaturated moiety and their antioxidant effects |
| Authors: |
Melford Chuka Egbujor; Brigitta Buttari; Elisabetta Profumo; Pelin Telkoparan-Akillilar; Luciano Saso |
| Contributors: |
Chuka Egbujor, Melford; Buttari, Brigitta; Profumo, Elisabetta; Telkoparan-Akillilar, Pelin; Saso, Luciano |
| Publication Year: |
2022 |
| Collection: |
Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: |
KEAP1; NRF2; Parkinson’s disease; anti-inflammatory; antioxidant; carbonyl; sulfinyl; sulfonyl; α,β-unsaturated moiety; Kelch-like ECH-associated protein 1; oxidative stre; signal transduction; NF-E2-related factor 2 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35955599; info:eu-repo/semantics/altIdentifier/wos/WOS:000839176600001; volume:23; issue:15; firstpage:1; lastpage:37; numberofpages:37; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; https://hdl.handle.net/11573/1652404 |
| DOI: |
10.3390/ijms23158466 |
| Availability: |
https://hdl.handle.net/11573/1652404; https://doi.org/10.3390/ijms23158466 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.76580B03 |
| Database: |
BASE |