3 research outputs found
New N,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation
A series of N,N-dimethylcarbamates containing a N,N-dibenzylamino moiety was synthesized
and tested to evaluate their ability to inhibit Acetylcholinesterase (AChE). The most active
compounds 4 and 8, showed 85 and 69% of inhibition at 50 mM, respectively. Furthermore,
some basic SAR rules were outlined: an alkyl linker of six methylene units is the best spacer
between the carbamoyl and dibenzylamino moieties; electron-withdrawal substituents on
aromatics rings of the dibenzylamino group reduce the inhibitory power. Compound 4
produces a slow onset inhibition of AChE and this is not due to the carbamoylation of the
enzyme, as demonstrated by the time-dependent inhibition assay of AChE with compound 4
and by MALDI-TOF MS analysis of trypsinized AChE inhibited by compound 4. Instead,
compound 4 could act as a slow-binding inhibitor of AChE, probably because of its high
conformational freedom due to the linear alkyl chain