| Title : New N,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation - De Vita_2016_J.Enzyme.Inhib.Med.Chem__1 |
| Author(s) : De Vita D , Pandolfi F , Ornano L , Feroci M , Chiarotto I , Sileno I , Pepi F , Costi R , Di Santo R , Scipione L |
| Ref : J Enzyme Inhib Med Chem , :1 , 2016 |
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Abstract :
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 muM, 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. |
| PubMedSearch : De Vita_2016_J.Enzyme.Inhib.Med.Chem__1 |
| PubMedID: 27594053 |
De Vita D, Pandolfi F, Ornano L, Feroci M, Chiarotto I, Sileno I, Pepi F, Costi R, Di Santo R, Scipione L (2016)
New N,N-dimethylcarbamate inhibitors of acetylcholinesterase: design synthesis and biological evaluation
J Enzyme Inhib Med Chem
:1
De Vita D, Pandolfi F, Ornano L, Feroci M, Chiarotto I, Sileno I, Pepi F, Costi R, Di Santo R, Scipione L (2016)
J Enzyme Inhib Med Chem
:1