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Phenothiazines: Nrf2 activation and antioxidant effects.
Melford C Egbujor1, Paolo Tucci2, Brigitta Buttari3
1Department of Chemistry, Federal University Otuoke, Otuoke, Nigeria.
Journal of Biochemical and Molecular Toxicology
|February 19, 2024
Summary
Phenothiazines (PTZs) are direct, non-electrophilic activators of the Nrf2 pathway, offering a safer alternative for reducing oxidative stress. This review highlights their potential as free radical scavengers for treating diseases linked to oxidative injury.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Phenothiazines (PTZs) demonstrate efficacy in modulating redox signaling and mitigating cellular oxidative injury.
- PTZs activate the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
- Existing electrophilic Nrf2 activators pose risks of "off-target" effects due to complex mechanisms.
Purpose of the Study:
- To provide the first comprehensive overview of phenothiazines (PTZs) as non-electrophilic Nrf2 activators.
- To explore the role of PTZs as free radical scavengers.
- To discuss the potential therapeutic applications of PTZs in oxidative stress-mediated diseases.
Main Methods:
- Literature review focusing on phenothiazines (PTZs) and their interaction with the Nrf2 pathway.
- Analysis of PTZs' mechanisms as direct, non-electrophilic modulators of Nrf2.
- Compilation of data on PTZs' free radical scavenging capabilities.
Main Results:
- Phenothiazines (PTZs) function as direct, non-electrophilic activators of the Nrf2 signaling pathway.
- PTZs exhibit significant free radical scavenging properties.
- These properties suggest therapeutic potential for PTZs in conditions associated with oxidative stress.
Conclusions:
- Phenothiazines (PTZs) represent a promising class of compounds for targeting the Nrf2 pathway.
- Their non-electrophilic nature and free radical scavenging abilities offer advantages over existing activators.
- Further research into PTZs could lead to novel therapeutic strategies for oxidative stress-related disorders.
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