Exploring the antioxidant potential of bis-1,2,3-triazolyl-N-phenylacetamides

Oxidative stress causes an imbalance between formation and accumulation of reactive oxygen species in cells and tissue, leading to various chronic and degenerative illnesses, viz. aging, cataract, cancer, rheumatoid arthritis, autoimmune disorders, and cardiovascular and neurodegenerative diseases. In this study, we have screened a library of bis-1,2,3-triazolyl-N-phenylacetamides (3a-z) for their in vitro antioxidant activity via 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. A detailed structure activity relationship study was undertaken to identify the key substitution contributing to the antioxidant activity followed by molecular docking study against enzyme myeloperoxidase (MPO). Myeloperoxidase is a heterodimeric, cationic, and glycosylated heme enzyme, which gets released under increased oxidative stress producing neutrophil oxidant, hypochlorous acid having the capacity to modify various biomolecules by chlorination and/or oxidation of sulfhydryl groups in proteins causing their inactivation and promoting tissue damage. The in silico binding affinity study could shed light on the binding modes of these molecules and further identify the thermodynamic interactions with active site residues governing the binding affinity. This in silico study could provide a platform for structure-based optimization of bis-1,2,3-triazolyl-N-phenylacetamides as potential modulators of pro-oxidative tissue injury pertubated by the MPO/H2O2/HOCl/HOBr system. Here, the ultimate study results illustrated that most of the derivatives were more active than standard antioxidant agent. Hence, this study also serves a significant contribution in the discovery of potent antioxidants in future research.

Automated summary

This study screened a library of bis-1,2,3-triazolyl-N-phenylacetamides for their antioxidant activity and investigated their binding affinity with myeloperoxidase. The results provided insights into the potential of these compounds as modulators of pro-oxidative tissue injury. The study also contributed significantly to the discovery of potent antioxidants for future research.