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 acetyl-cholinesterase 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, H-1-NMR, C-13-NMR, elemental analysis and HRMS spectra. The inhibition profiles of the synthesized compounds on AChE were researched by comparing their IC(50 )and K-I 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. (C) 2022 Elsevier B.V. All rights reserved.