title: Specific targeting of acetylcholinesterase and butyrylcholinesterase recognition sites. Rational design of novel, selective, and highly potent cholinesterase inhibitors.
abstract: Tacrine-based AChE and BuChE inhibitors were designed by investigating the topology of the active site gorge of the two enzymes. The homobivalent ligands characterized by a nitrogen-bridged atom at the tether level could be considered among the most potent and selective cholinesterase inhibitors described to date. The nitrogen-containing homobivalent ligands 3e,g and the sulfur-containing 3h validated the hypothesis of extra sites of interaction in the AChE and BuChE active site gorges.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università di Siena, via Aldo Moro, 53100 Siena, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Savini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gaeta
authors.forename: Caterina
authors.initials: C
authors.lastname: Fattorusso
authors.forename: Bruno
authors.initials: B
authors.lastname: Catalanotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.forename: Luisa
authors.initials: L
authors.lastname: Chiasserini
authors.forename: Cesare
authors.initials: C
authors.lastname: Pellerano
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Dawn
authors.initials: D
authors.lastname: McKissic
authors.forename: Ashima
authors.initials: A
authors.lastname: Saxena
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002800:Cholinesterase Inhibitors; D008024:Ligands; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase