Zia_2022_Bioorg.Chem_121_105658

A variety of diarylpyrazole derivatives III-VI were synthesized and structurally characterized using FTIR, (1)H and (13)C NMR spectroscopy, and in case of compound VIb by X-ray single crystal analysis. The in vitro biological studies revealed that seven of the diarylpyrazole derivatives IIIa, IIIb, IIId, IIIe, IVa, IVb and IVd are highly potent inhibitors of acetylcholinesterase enzyme with IC(50) values of 0.48 +/- 0.092 microg/mL, 0.45 +/- 0.093 microg/mL, 0.30 +/- 0.014 microg/mL, 0.59 +/- 0.072 microg/mL, 0.29 +/- 0.084 microg/mL, 0.56 +/- 0.010 microg/mL and 0.28 +/- 0.096 microg/mL, respectively. All these seven products were more potent than the standard drug, donepezil (IC(50) = 0.73 +/- 0.015 microg/mL), while compounds IIIc (0.67 +/- 0.099 microg/ml) and VIa (0.66 +/- 0.069 microg/ml) are almost equipotent to the donepezil. Particularly, compounds IVa and IVd are highly active acetylcholinesterase enzyme inhibitors, demonstrating more than two-fold inhibitory activity than the reference inhibitor. Molecular docking studies were carried out to identify the possible binding modes of the diarylpyrazoles within the active pocket of the enzymes. The docking interactions of the synthesized compounds with acetylcholinesterase also provided high docking scores. These results clearly indicate the potential of these compound as powerful lead molecules for further investigations.