Bioactivity of selenium‐containing pyridinium salts: Prospecting future pharmaceutical constituents to treat liver diseases involving oxidative stress

Redox imbalance leads to oxidative stress that causes irreversible cellular damage. The incorporation of the antioxidant element selenium (Se) in the structure of pyridinium salts has been used as a strategy in chemical synthesis and can be useful in drug development. We investigated the antioxidant activity of Se‐containing pyridinium salts (named Compounds 3A, 3B, and 3C) through in vitro tests. We focused our study on liver protein carbonylation, liver lipoperoxidation, free radical scavenging activity (1,1‐diphenyl‐2‐picryl‐hydrazil [DPPH]; 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid [ABTS]), and enzyme‐mimetic activity assays (glutathione S‐transferase [GST]‐like; superoxide dismutase [SOD]‐like). In addition, 2‐(4‐chlorophenyl)‐2‐oxoethyl)‐2‐((phenylselanyl)methyl)pyridin‐1‐ium bromide (3C) was selected to evaluate the acute oral toxicity in mice due to the best antioxidant profile. The three compounds were effective in reducing the levels of protein carbonylation and lipoperoxidation in the liver in a µM concentration range. All compounds demonstrated scavenger activity of DPPH and ABTS radicals, and GST‐like action. No significant effects were detected in the SOD‐like assay. Experimental data also showed that the acute oral treatment of mice with Compound 3C (50 and 300 mg/kg) did not cause mortality or change markers of liver and kidney functions. In summary, our findings reveal the antioxidant potential of Se‐containing pyridinium salts in liver tissue, which could be related to their radical scavenging ability and mimetic action on the GST enzyme. They also demonstrate a low toxicity potential for Compound 3C. Together, the promising results open space for future studies on the therapeutic application of these molecules.