(E)-N'-(4-methoxybenzylidene)-2-((5-phenyl-1H-pyrazol-3-yl)oxy)acetohydrazide as potential antidiabetic agent

In this study, we synthesized (E)-N'-(4-methoxybenzylidene)-2-((5-phenyl-1H-pyrazol-3-yl)oxy)acetohydrazide (MBPA), a novel compound exhibiting significant inhibitory activity against α-amylase and α-glucosidase enzymes. The target compound was obtained through a condensation reaction between 2-((5-phenyl-1H-pyrazol-3-yl)oxy)acetohydrazide and 4-methoxybenzaldehyde. Structural confirmation was achieved using comprehensive spectroscopic techniques, including 1H NMR, 13C NMR, FT-IR, and HRMS-ESI. Additionally, single-crystal X-ray diffraction (XRD) analysis was performed to elucidate the molecular structure. The molecular geometry, electronic properties, and reactivity descriptors of the compound were investigated using density functional theory (DFT) at the B3LYP/6–311++G(d,p) level. Key analyses included MEP, NBO, QTAIM, and NCI. Additionally, Hirshfeld surface analysis was employed to characterize intermolecular interactions within the MBPA crystal structure, utilizing normalized contact distance (dₙₒᵣₘ) surfaces and 2D fingerprint plots. MBPA was evaluated for its antihyperglycemic potential through in vitro assays. The compound demonstrated significant inhibitory effects against both α-glucosidase (IC50 = 68.99 ± 0.85 µM) and α-amylase (IC50 = 174.1 ± 1.85 µM), outperforming the standard drug acarbose (IC50 values of 98.12 ± 2.10 µM and 126.5 ± 2.10 µM, respectively). In addition, molecular docking studies were performed to investigate the interaction between the ligand (MBPA) and receptor proteins, α-glucosidase (PDB code: 3W37) and α-amylase (PDB code: 3CPU).