Antioxidant evaluation of novel 3-Aryl-5-phenyloxy-1,2,4-oxadiazoles as radical scavengers: Synthesis, characterization, and ADME studies

Abstract

Cell function depends on redox homeostasis, and several diseases are linked to its disruption. The relative amounts of reduced and oxidised glutathione play a major role in controlling redox balance. Redox equilibrium is essential for a number of physiological functions, including protein folding and cell signalling. Thus, redox imbalance has been linked to a number of clinical illnesses, including diabetes, cancer, and neurodegenerative diseases. Here, we designed and synthesized a new library of 3, 5-diaryl-1,2,4-oxadiazole derivatives, evaluated by scavenging the dangerous free radicals. The produced oxadiazoles are all examined by spectroscopic and micro-analytical techniques. Three assays were used to assess the antioxidant properties: total antioxidant (FRAP), DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals, and nitric oxide. When nitric oxide, DPPH, and FRAP were combined, the results were nearly same. Key findings revealed that compounds 12 , 10 , and 13 exhibited superior NO scavenging activity with IC 50 values of 35.59 ± 1.3, 37.41 ± 1.1, and 40.54 ± 1.3 μM, respectively. DPPH assay results indicated potent radical scavenging activity, with IC 50 values of 67.08 ± 1.1 to 99.94 ± 1.1 μM. In the FRAP assay, compounds 15 , 18 , 11 , 10 , and 12 demonstrated the highest antioxidant activities, which were consistent with the results of the other assays. Computational predictions of the physicochemical attributes, pharmacokinetic profiles, and drug-likeness data of all the synthesized compounds indicated that our hits may be introduced as drug-like candidates because they showed appropriate criteria in medicinal chemistry and drug-likeness values which hopefully can alleviate poor biopharmaceutical properties of many antioxidants.