biostudies-literatureAloui MKing Saud University, Riyadh, Saudi Arabia.15910https://www.ebi.ac.uk/biostudies/studies/S-EPMC12059048biostudies-literatureUnknown15(1)Alzheimer's disease (AD) necessitates innovative therapeutic approaches that target its multifaceted pathology. This study investigates a series of 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives as potential multi-target ligands for AD, aiming to simultaneously inhibit acetylcholinesterase (AChE) and amyloid-beta (Aβ) aggregation. To assess the therapeutic potential of these compounds, we employed a comprehensive computational approach, incorporating 2D-QSAR modeling, molecular dynamics simulations, molecular docking, and ADMET property analysis. Based on these analyses, we designed 13 novel pyridazine derivatives exhibiting favorable interactions with key AD-related proteins, enhanced dynamic stability within protein binding sites, and adherence to established drug-likeneScientific reportsIn silico design of novel pyridazine derivatives as balanced multifunctional agents against Alzheimer's disease.PMC12059048Project (No. RSPD2024R566)Abuelizz HAAloui MMujwar SEl Fadili MEr-Rahmani SMenana EEr-Rajy MZarougui SfalseIn silico design of novel pyridazine derivatives as balanced multifunctional agents against Alzheimer's disease.Alzheimer's disease (AD) necessitates innovative therapeutic approaches that target its multifaceted pathology. This study investigates a series of 2-aminoalkyl-6-(2-hydroxyphenyl)pyridazin-3(2H)-one derivatives as potential multi-target ligands for AD, aiming to simultaneously inhibit acetylcholinesterase (AChE) and amyloid-beta (Aβ) aggregation. To assess the therapeutic potential of these compounds, we employed a comprehensive computational approach, incorporating 2D-QSAR modeling, molecular dynamics simulations, molecular docking, and ADMET property analysis. Based on these analyses, we designed 13 novel pyridazine derivatives exhibiting favorable interactions with key AD-related proteins, enhanced dynamic stability within protein binding sites, and adherence to established drug-likene2025-01-01T00:00:00Z2025 May2026-06-02T12:09:02.395Z2026-04-18T03:11:06.092ZS-EPMC120590484033560710.1038/s41598-025-98182-x