Synthesis and Biological Evaluation of Some Piperidine Hydrazide-Hydrazone Derivatives as AChE/BuChE Inhibitors

Parlar S. , Sayar Gümüş G., Tarikoğulları Doğan A. H. , Sözer Karadağlı L. S. , Alptüzün V.

VII EFMC International Symposium on Advances in Synthetic and Medicinal Chemistry, Vienna, Austria, 27 - 31 August 2017, pp.349

  • Publication Type: Conference Paper / Summary Text
  • City: Vienna
  • Country: Austria
  • Page Numbers: pp.349


Alzheimer’s disease (AD) is a neurodegenerative disorder which is characterized by progressive and irreversible cognitive impairment followed by memory loss [1]. The etiology of AD is still not fully known but reduced levels of the neurotransmitter acetylcholine (ACh) in the brain is believed to be one of the major causes of cognitive function damage, loss of memory and other possible symptoms of AD [2]. To date, one of the effective therapeutic strategies to treat AD is to maintain the levels of ACh by inhibiting the enzyme acetylcholinesterase (AChE) [3]. AChE and butyrylcholinesterase (BuChE) are the two types of cholinesterase enzyme. They both play important roles in the regulation of ACh levels. It is reported in the literature that the elevated BuChE may act as a compensatory mechanism for ACh hydrolysis and ACh regulation may become increasingly dependent on BuChE as AD progresses [4].On the other hand, oxidative stress has been considered as a mechanism involved in the pathogenesis of AD. It is important to improve the antioxidant defence system of the brain tissue against the oxidative stress that has a role in the neurodegenerative diseases [5].In the present study, a series of piperidine hydrazide-hydrazone derivatives (Fig 1) were synthesized, purified and their structures were identified by spectroscopic methods. AChE and BuChE inhibitory activities were evaluated in vitro by using colorimetric Ellman’s method [6]. Some of the compounds displayed selective AChE inhibitory activity while some of the compounds displayed selectivity against BuChE enzyme. The antioxidant activity of the title compounds were also tested by DPPH and ABTS methods.