Design Synthesis Biological Evaluation and MolecularModeling of 1H Benzimidazole Derivatives asAcetyl Butyrylcholinesterase Inhibitors


Çoban G. , Sarıkaya G. , Alpan A. S. , Parlar S. , Tarikoğulları Doğan A. H. , Alptüzün V.

2nd International BAU Drug Design Congress, İstanbul, Türkiye, 17 - 19 Nisan 2014, ss.120

  • Basıldığı Şehir: İstanbul
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.120

Özet

Alzheimer’s disease (AD), the most common dementia in elderly people, is a neurodegenerative disorder of the central nervous system. The cholinergic system in Alzheimer patients’ brains is dramatically affected. The treatment of AD with cholinesterase inhibitors is based on the cholinergic hypothesis.1 Acetylcholinesterase (AChE) inhibitors can increase the level of neurotransmitter in the synaptic cleft, thereby improving cognition level of mild to moderate AD patients.2 However, as AChE activity is greatly reduced in specific regions of the brain, butyrylcholinesterase (BuChE) activity increases due to compensation mechanism.3, 4 In our previous study, a series of N-{2-[4-(1H-benzimidazole-2-yl)phenoxy]ethyl}substituted amine derivatives bearing p-ethoxy side chain were designed and tested for their cholinesterase inhibitor activity.5 In this study, in order to investigate the contribution of the positional change to the inhibitor activity,1H-benzimidazole derivatives bearing o-ethoxy moiety were synthesized. AChE and BuChE inhibitor activities were evaluated in vitro by using Ellman’s method.6 According to the activity results, generally, the compounds displayed more BuChE inhibitor activity than AChE. Molecular docking studies were also carried out.