Furan-oxadiazole hybrids as promising antioxidants: Synthesis, characterization, ADME and molecular docking studies on peroxiredoxin-2

Abstract

The study involves the synthesis and characterization of a novel series of furan-based compounds 1–9 incorporating strategic modifications with isatin, pyrazole, and oxadiazole motifs. The synthesized compounds were characterized and assigned with different spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR and mass spectra. Antioxidant screening assays using the DPPH radical scavenging method revealed that the oxadiazole derivative 9 exhibited exceptional antioxidant activity, with an EC50 value of 0.0038 mM, attributed to the oxadiazole ring's favourable electron delocalization and radical stabilization properties. Molecular docking simulations with the Peroxiredoxin-2 (Prdx-2) crystal structure (PDB: 5IJT) predicted favourable binding interactions for the synthesized compounds, with docking scores ranging from -6.1629 to -7.9878 kcal/mol. The sugar moieties facilitated hydrogen bonding interactions with key active site residues, while the furan and phenyl rings contributed to π-hydrogen interactions. Furthermore, in silico ADME prediction studies assessed the drug-likeness and pharmacokinetic properties of the compounds, identifying promising lead candidates for further optimization and development as potential antioxidant therapeutics targeting Prdx-2.