title: Studies on a new series of THA analogues: effects of the aromatic residues that line the gorge of AChE.
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.
authors.affiliation: Istituto di Chimica e Chimica Clinica, Facoltà di Medicina, UCSC, Rome, Italy. m.pomponi@uniserv.ccr.rm.cnr.it
authors.forename: M
authors.initials: M
authors.lastname: Pomponi
authors.forename: M
authors.initials: M
authors.lastname: Marta
authors.forename: A
authors.initials: A
authors.lastname: Colella
authors.forename: S
authors.initials: S
authors.lastname: Sacchi
authors.forename: M
authors.initials: M
authors.lastname: Patamia
authors.forename: F
authors.initials: F
authors.lastname: Gatta
authors.forename: F
authors.initials: F
authors.lastname: Capone
authors.forename: A
authors.initials: A
authors.lastname: Oliverio
authors.forename: F
authors.initials: F
authors.lastname: Pavone
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000187:drug effects*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004593:Electrophorus; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D013619:Tacrine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D014101:Torpedo
chemical_list: D002800:Cholinesterase Inhibitors; D013619:Tacrine; D000110:Acetylcholinesterase