New derivatives of imine as inhibitors of acetylcholinesterase (AChE): Synthesis, biological evaluation, antioxidant activity and molecular docking

Alzheimer’s diseases (AD) is a neurodegenerative disorder of the central nervous system that connected to memory loss, cognitive impairment. There are some drugs that decreased symptoms of AD patients. The AD is associated with oxidative stress condition and increased free radical, protein oxidation in the brain of patients. AChE plays an important role in the AD that hydrolyzes Acetylcholine (Ach) and it is a member of the serine hydrolase family that belonging to the α/β hydrolase. One of the biochemical symptoms of the AD is the reduction of Ach. Inhibitors of AChE are the most positive treatment strategy for AD therapy that resulted in improving the cognitive and memory. New derivatives of 2-chloro-3-hydrazino pyrazine were designed and synthesized that show the inhibitory activity of AChE for developing AD therapeutics. Novel imine compounds of hydrazino pyrazine with 4-methoxy benzaldehyde (S1), chromen-3-benzaldehyde (S2), 3-hydroxybenzaldehyde (S3) were produced by reflux column and purified by recrystallization. FT-IR and NMR analysis were performed to characterize the structure of compounds. The inhibitory activities of S1, S2, S3 were evaluating by Ellman’s method. Both compounds were able to reduce the DPPH radical. They had antioxidant activity but S2 had more antioxidant properties. Molecular docking of these synthetic compounds was carried out and results of the interaction between synthetic compounds and enzyme were confirmed.

Keywords:

Acetylcholinesterase (AChE) , Acetylcholine (Ach) , Inhibitors