STUDIES ON A NEW SERIES OF THA ANALOGS - EFFECTS OF THE AROMATIC RESIDUES THAT LINE THE GORGE OF ACHE

A series of N-monoalkylsubstituted 1,2,3,4-tetrahydro-9-aminoacridines have been prepared after modelling simulation of the AChE-inhibitor c omplex. Molecular modelling has predicted a number of hydrophobic resi dues to be involved in the catalytic mechanism of this interaction bet ween the binding sites of AChE and this series of aminoacridines, In t hese compounds the acridine moiety becomes sandwiched between the ring s of PHE330 and TRP84, In particular, the alkyl chain shows the import ant role of aromatic groups as binding sites, Their in vitro inhibitor y properties (enzyme from Electrophorus electricus) confirm the aromat ic groups as a general and significant characteristic of the mechanism of AChE inhibition. (C) 1997 Federation of European BiochemicaI Socie ties.