Phenothiazines: Nrf2 activation and antioxidant effects

Abstract

Phenothiazines (PTZs) are an emerging group of molecules showing effectiveness toward redox signaling and reduction of oxidative injury to cells, via the activation on Kelch‐like ECH‐associated protein 1/nuclear factor erythroid 2‐related factor 2 (Nrf2). Although several electrophilic and indirect Nrf2 activators have been reported, the risk of “off‐target” effect due to the complexity of their molecular mechanisms of action, has aroused research interest toward non‐electrophilic and direct modulators of Nrf2 pathway, such as PTZs. This review represents the first overview on the roles of PTZs as non‐electrophilic Nrf2 activator and free radical scavengers, as well as on their potential therapeutic effects in oxidative stress‐mediated diseases. Here, we provide a collective and comprehensive information on the PTZs ability to scavenge free radicals and activate the Nrf2 signaling pathway, with the aim to broaden the knowledge of their therapeutic potentials and to stimulate innovative research ideas.

New Isomeric Dipyridothiazine Dimers — Synthesis, Structural Characterization and Cytotoxicity Screening

“…These drugs are still used in medical treatment to this day [1]. Scientific research in the area of phenothiazines is constantly being carried out, revealing many further interesting pharmacological activities, including: anticancer [6][7][8][9][10], antimicrobial [11,12], antifungal [13], antiviral [14,15], antioxidant [16] or reversal of multidrug resistance activities [17]. These topics are rich resulting in numerous review papers published each year around the world [18][19][20][21][22].…”