Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme

Alzheimer's disease is a neurological disease characterized by the destruction of brain cells. In this disease,which causes a decrease in thought, memory and behavioral functions, the symptoms appear gradually with age. Inthis study, inhibition of acetylcholinesterase enzyme which is an important target in accordance with the cholinergichypothesis, was studied. New 3(2H)pyridazinone-triazole derivatives were synthesized, confirmed by 1H-NMR, 13CNMR,HRMS analysis and their IC50 and Ki values were studied. The inhibition constants (Ki) of the compounds againstthe AChE enzyme ranged from 2.35 ± 0.18 to 5.15 ± 0.46 μM. The compound with the best inhibitory properties wascompound 6d with a Ki value of 2.35 ± 0.18 μM. In addition, to support the experimental data, molecular docking studieswere carried out with 6b, 6d, 6e and 6f compounds with AChE crystal structure (PDB ID:4M0E).