Screening of new morpholine dithiocarbamate derivatives bearing benzimidazole moiety for anticholinesterase potential

Abstract

Alzheimer’s disease (AD) is basically associated with disturbances of cholinesterase metabolism which result in acetylcholine deficiency. Target of acetylcholinesterase (AChE) inhibitors used in symptomatic therapy of disease is to increase of ACh levels. Consequently, cholinesterase inhibitors were developed to increase acetylcholine is to inhibit AChE and butrylcholinesterase (BuChE). Studies demonstrate the clinical importance of dual inhibitors that inhibit not only the acetylcholinesterase enzyme but also the butyrylcholinesterase enzyme.

In recent years, benzimidazoles have attracted particular interest owing to their anticolinesterase activity. In this manner, we have synthesized benzimidazole and morpholine including compounds (2a-i). Final compounds were achieved with the reaction of (benzimidazol-2-yl) methyl morpholine-4-carbodithioate and α-bromoacetophenone derivatives in acetone at room temperature with stirring. Inhibition effects of novel morpholine dithiocarbamates (2a-i) were tested on AChE and BuChE. Compound 2d demonstrated dual inhibitory activity on AChE and BuChE (78±1,56, 70,71±1,53, respectively), with the lowest cytotoxicity to normal cell line.