A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE).

Abstract

The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition wasemployed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The hetero-dimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase(BuChE). The heterodimers displayed preferential inhibition (>9) of BuChE over AChE in the micromolarconcentration range (IC50¼7–50mM). For the most potent inhibitor of BuChE, Cornish-Bowden plots wereused, which demonstrated that it behaves as a mixed inhibitor. Modelling studies of the same inhibitordemonstrated that the benzotriazole and 1-deoxynojirimycin moiety is accommodated in the peripheralanionic site and catalytic anionic site, respectively, of AChE. The binding mode to BuChE was different asthe benzotriazole moiety is accommodated in the catalytic anionic site.