3(2H)-pyridazinone derivatives: Synthesis, in-silico studies, structure-activity relationship and in-vitro evaluation for acetylcholinesterase enzyme inhibition

New ten compounds bearing pyridazinone ring (5a–j) were designed and synthesized as acetylcholinesterase inhibitors. The new derivatives were acquired via the reaction of propionohydrazides with substituted/nonsubstituted sulphonylchlorides. The structures of the synthesized compounds were explained using FT-IR, 1H-NMR, 13C-NMR, elemental analysis and HRMS spectra. The inhibition profiles of the synthesized compounds on AChE were researched by comparing their IC50 and KI values. According to the activity studies, all the compounds showed significant inhibitory activity against AChE relative to the reference compound Tacrine. The compound 5g showed the best acetylcholinesterase inhibitory effect with a KI value of 11.61 ± 0.77 nM. For all compounds, the parameters of the interaction points on the receptor side were determined on the ligand basis with the 4D-QSAR model. The synthesized pyridazinone derivatives, 5(a-j), were screened for their acetylcholinesterase inhibitory potential, and the results determined that among the series, compounds 5g, 5f and 5j showed the best inhibition, respectively. For anti-Alzheimer activities, 5g, 5f and 5j compounds were performed in silico studies to understand the binding site, binding energy properties in molecular docking. © 2022