Synthesis of unsymmetrical thiosulfonate derivatives and acetylcholinesterase (AChE) and butylcholinesterase (BChE) examination of the effect on enzymes

In this thesis, unsymmetrical thiosulfonate derivatives were synthesized, and their inhibitory effects on AChE and BChE enzymes were investigated. Thiosulfonates are compounds that play critical roles in biochemical processes, exhibiting antioxidant properties by neutralizing free radicals and reactive oxygen species, thereby protecting cells against oxidative stress and regulating the functionality of enzymes involved in redox reactions. AChE is considered an important molecular target for the detection, diagnosis, and treatment of various diseases. Natural compounds that inhibit AChE and BChE enzymes are being explored as potential therapeutic agents. Notably, plants such as garlic, which are rich in organosulfur compounds, are thought to possess these inhibitory properties. The ability of thiosulfonate derivatives to induce the sulfonation of thiol groups in certain enzymes may contribute to AChE inhibition. In this context, the synthesis of unsymmetrical thiosulfonate derivatives can facilitate the development of cholinesterase inhibitors. These inhibitors play a significant role in the treatment of Alzheimer's disease and other neurological disorders. In this study, potassium p-toluenethiosulfonate was reacted with various p-substituted benzyl halides in the presence of DMF at room temperature to obtain unsymmetrical thiosulfonate derivatives, which were characterized using ¹H-NMR and ¹³C-NMR spectroscopy. Furthermore, the inhibitory effects of the synthesized compounds were evaluated, and their IC50 values and Kᵢ constants were calculated and presented.