Paper Title
Synthesis and Biological Activity Evaluation of New Benzimidazole-Piperazine Derivatives as Anticholinesterase Agents

Abstract
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease characterized clinically by memory and cognitive deficits. It is primarily seen in the elderly population and is the most common cause of dementia. The most important pathological features of Alzheimer's disease are β-amyloid (Aβ) extracellular plaques, intracellular neurofibrillary tangles (NFT) resulting from excessive phosphorylation of tau protein, and loss of cholinergic neurons in the basal forebrain. Inadequate cholinergic transmission plays an important role in the development of cognitive, functional and behavioral symptoms in Alzheimer's disease. Therefore, treatments are generally planned to increase the function of the cholinergic system either with receptor agonist or acetylcholinesterase inhibitors (AChEI). The aim of this study was to investigate the inhibition of eight new benzimidazole-piperazine derivatives (2a-2h) on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activity, which are likely to be used in the treatment of Alzeheimer's disease (AD). The structures of synthesized compounds were confirmed via 1H and 13C NMR spectroscopic methods. Anticholinesterase enzyme inhibition assay of the compounds was determined spectrophotometrically by the Ellman method. None of the compounds in the series showed remarkable activity on BChE enzyme. In terms of AChE enzyme inhibition potency, compound 2g was found as the most active derivative in the series with IC50 value of 0.2118±0.008 µM. Keywords - Alzheimer’ Disease, Amyloid Plaques, Cholinergic Hypothesis, Benzimidazole, Piperazine