Evaluation of Antioxidant Activities of Novel Tetralone-Derived Triazoles Derivatives: Synthesis and in silico Studies

Abstract

In present study, twelve novel tetralone-linked triazole derivatives (6a-l) were synthesised and structurally characterised using ¹H NMR, ¹³C NMR and mass spectrometric techniques. The antioxidant potential of the synthesised compounds was evaluated through 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and lipid peroxidation (LPO) inhibition assays. Among the tested derivatives, compounds 6e, 6h, 6d and 6i consistently exhibited the strongest antioxidant activities. In the DPPH assay, compound 6e demonstrated the highest radical-scavenging capacity with 79.9% inhibition at 120 µM, followed by 6h (64.3%), 6d (56.18%) and 6i (51.8%), reflecting a clear dose-dependent response. These findings were further supported by the LPO assay, where the same four derivatives showed significant protection against oxidative damage to lipid membranes. At 120 µM, compound 6e displayed the most potent activity with showing 79.9% inhibition, while 6h, 6d and 6i exhibited 64.3%, 60.1% and 52.12% inhibition, respectively. The corresponding IC₅₀ values (24-30 µM) further confirmed their strong ability to suppress the chain-propagation phase of lipid peroxidation. Moreover, the molecular docking studies were performed to investigate the interactions of the synthesised derivatives with the oxidoreductase protein (PDB ID: 3NM8) and their pharmacokinetic profiles were predicted using in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis.