Novel Pyridazinone‐1,3,4‐oxadiazole Hybrids as Antioxidant and Antidiabetic Agents: Synthesis, Biological Evaluation, ADMET, and Molecular Docking Studies

Abstract Pyridazin‐3(2H)‐one and 1,3,4‐oxadiazole have emerged as promising lead candidates for inhibiting glucose‐metabolizing enzymes, such as α‐glucosidase and α‐amylase. Furthermore, several investigations have demonstrated their strong antioxidant activities. In the present work, we report the synthesis of novel molecules hybridizing a pyridazin‐3(2H)‐one ring and a 1,3,4‐oxadiazole ring. The compounds were screened for their antioxidant activity. In DPPH and ABTS assays, compound O7 exhibited the most potent antioxidant activity, with IC 50 values of 21.32 ± 0.30 µmol/mL and 11.52 ± 0.10 µM, respectively, higher than that of sodium ascorbate. In the FRAP assay, compounds O3 (70.51 ± 3.12 µM) and O7 (61.53 ± 0.67 µM) showed superior iron‐reducing activity. As regards their antidiabetic activity, compounds O3 and O7 showed potent α‐amylase inhibitory activity with IC 50 values of 99.93 ± 1.71 µM and 93.12 ± 3.10 µM, respectively. Compound O3 also possessed the highest α‐glucosidase Inhibition activity, with an IC 50 of 22.06 ± 0.24 µM, far higher than acarbose. The molecular docking study also supported that the O3 compound shows maximum binding interaction on α‐amylase and α∖glucosidase. The binding of O3 to these enzymes is through various hydrophobic and hydrogen bonds, responsible for its good stability and justifying its strong inhibitory action.