Synthesis of novel pyridazine derivatives and evaluation of their biological activities

Synthesis of Novel Pyridazine Derivatives and Evaluation of Their Biological Activities Aim: Alzheimer's disease is a serious health problem worldwide. It is one of the most common neurodegenerative diseases in the elderly population and is becoming an increasingly significant public health issue due to the aging population. Current treatment approaches are not aimed at curing the disease or halting its progression; rather, they focus on controlling the symptoms. Furthermore, the effectiveness of currently available medications is limited, and they have varying side effect profiles. For all these reasons, research into developing more effective anti-Alzheimer's agents is being intensively pursued. The cholinergic hypothesis proposed for the treatment of the disease aims at inhibiting the AChE and BChE enzymes. This thesis aims to synthesize compounds with the structure "3(2H)-pyridazinone" and investigate their cytotoxic effects. Material and method: This thesis study involved the synthesis and cytotoxic evaluation of 6 new compounds. The structures of the compounds were elucidated using information obtained from 1H-NMR, 13C-NMR, and mass spectrometry. The in vitro cytotoxic effects of the compounds against the venous endothelial cell line (HUVEC) have been determined. Results: As a result of the cholinesterase activity studies conducted, IC50 and Ki values of the synthesized compounds in the vein endothelial cell line (HUVEC) were calculated. Conclusion: All synthesized compounds were found to be less toxic than the reference drug. All molecules, especially compound B4, were observed to exhibit a strong inhibition profile when compared to the reference drug. Keywords: 3(2H)-pyridazinone, AChE, Alzheimer's disease, BChE