Synthesis Of New Thiadiazole-Dithiocarbamate Derivatives As Acetylcholinesterase Inhibitors
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease characterized clinically by memory and cognitive deficits. Inadequate cholinergic transmission plays an important role in the development of cognitive, functional and behavioral symptoms in AD. Therefore, treatments are generally planned to increase the function of the cholinergic system either with receptor agonist or acetylcholinesterase inhibitors (AChEI). Based on the cholinergic hypothesis, the most successful approach to treat AD is to restore the level of acetylcholine (ACh). In this paper a series of new 1,3,4-thiadiazole derivatives has been designed, synthesized and evaluated as the acetyl- and butyrylcholinesterase (AChE and BChE) inhibitors. The structures of synthesized compounds were confirmed via 1H and 13C NMR spectroscopic methods. The modified Ellman’s colorimetric method was used for searching ChE enzymes inhibitory activity. None of the compounds in the series showed good activity on BChE enzyme. In terms of AChE enzyme inhibition potency, compounds 3g and 3h were found as the most active derivatives in the series with IC50 values of 0.1986±0.006 µM and 0.2150±0.009, respectively.
Index Terms: Alzheimer’ Disease, Cholinesterase Inhibitors, Thiadiazole, Piperazine, Dithiocarbamate.