Studies on a new series of THA analogues: Effects of the aromatic residues that line the gorge of AChE

Massimo Pomponi, Maurizio Marta, Annalisa Colella, Silvia Sacchi, Maria Patamia, Franco Gatta, Francesca Capone, Alberto Oliverio, Flaminia Pavone

Research output: Contribution to journalArticlepeer-review

Abstract

A series of N-monoalkylsubstituted 1,2,3,4-tetrahydro-9-aminoacridines have been prepared after modelling simulation of the AChE-inhibitor complex. Molecular modelling has predicted a number of hydrophobic residues to be involved in the catalytic mechanism of this interaction between the binding sites of AChE and this series of aminoacridines. In these compounds the acridine moiety becomes sandwiched between the rings of PHE330 and TRP84. In particular, the alkyl chain shows the important role of aromatic groups as binding sites. Their in vitro inhibitory properties (enzyme from Electrophorus electricus) confirm the aromatic groups as a general and significant characteristic of the mechanism of AChE inhibition.

Original languageEnglish
Pages (from-to)155-160
Number of pages6
JournalFEBS Letters
Volume409
Issue number2
DOIs
Publication statusPublished - Jun 9 1997

Keywords

  • Acetylcholinesterase catalysis
  • Acetylcholinesterase inhibitors
  • Acetylcholinesterase mechanism
  • Tacrine analogues

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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