Specific targeting of acetylcholinesterase and butyrylcholinesterase recognition sites. Rational design of novel, selective, and highly potent cholinesterase inhibitors.
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.
Savini
Luisa
L
Dipartimento Farmaco Chimico Tecnologico, Università di Siena, via Aldo Moro, 53100 Siena, Italy.
Gaeta
Alessandra
A
Fattorusso
Caterina
C
Catalanotti
Bruno
B
Campiani
Giuseppe
G
Chiasserini
Luisa
L
Pellerano
Cesare
C
Novellino
Ettore
E
McKissic
Dawn
D
Saxena
Ashima
A
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
D002800:Cholinesterase Inhibitors; D008024:Ligands; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase