Synthesis, X-ray, Hirshfeld surface, DFT, non-covalent interaction, antihyperglycemic activity and molecular docking studies of (E)-N'-(2-chlorobenzylidene)-2-((5-phenyl-1H-pyrazol-3-yl)oxy) acetohydrazide

In this work, a novel (E)-N'-(2-chlorobenzylidene)-2-((5-phenyl-1H-pyrazol-3-yl)oxy)acetohydrazide (CBPA) as potent alpha-amylase and alpha-glycosidase inhibitors was synthesized by condensation of 2-((5-phenyl-1H-pyrazol-3-yl) oxy)acetohydrazide with 2-chlorobenzaldehyde. The novel compound was fully characterized by FT-IR, 1H NMR, 13C NMR, HRMS-ESI spectral studies and single crystal XRD analysis. Crystal packing is stabilized by N1-H1N1 & sdot;& sdot;& sdot;O2i, N3-H1N3 & sdot;& sdot;& sdot;O2ii, C2-H2A & sdot;& sdot;& sdot;Cliii, and C17-H17A & sdot;& sdot;& sdot;N2 iv intermolecular hydrogen bonds. Hirshfeld surface analysis (dnorm surfaces and 2D fingerprint plots) was used to quantify the intermolecular interactions of CBPA crystal structure. Molecular geometry, reactivity parameters and electronic properties such as MEP, NBO, NLO, and FMO have been described using the DFT method at the B3LYP/6-311++G(d,p) level. Moreover, CBPA was investigated in vitro for their antihyperglycemic activity, and the results showed that the title compound exhibits remarkable inhibitory activity against alpha-glucosidase and alpha-amylase, with IC50 values of 33.36 +/- 0.89 and 89.85 +/- 0.08 mu M, respectively, compared with the reference drug acarbose. (IC50(alpha-glucosidase) = 98.12 +/- 2.10 mu M, IC50(alpha-amylase) = 126.5 +/- 2.10). Additionally, the molecular docking study was conducted to investigate the interaction between the ligand (CBPA) and receptor proteins, alpha-glucosidase (PDB = 3A4A) and alpha-amylase (PDB: 2GJP).