Synthesis of New Piperidine-Hydrazide Derivatives and Evaluation of their in Vitro Enzyme Activity
Alzheimer’s disease (AD) has an insidious onset and its progression is characterized by memory dysfunction and cognitive disturbances, such as problems recalling familiar names and objects and/or behavioral changes. Loss of short-term memory and impaired visuospatial orientation are typical early symptoms of the disease. As AD progresses there is a general decline of multiple cognitive functions related to daily activities. Ultimately patients become very dependent on caregivers. The lack of treatment has led researchers to work on this subject. The aim of this study was to investigate the inhibition of three new piperidine-hydrazide derivatives (3a-3c) 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 significant activity on BChE enzyme. In terms of AChE enzyme inhibition potency, compound 3a was found as the most active derivative in the series with IC50 value of 0.1856±0.006 µM.
Keywords - Alzheimer’ Disease, in Vitro Enzyme Inhibition, Piperidine, Hydrazide