Cage amines as the stopper inhibitors of cholinesterases.
Cage amines 1-4 are potent peripheral anionic site-bound reversible inhibitors of both acetylcholinesterase and butyrylcholinesterase. Cage amines 1-3 are selective butyrylcholinesterase inhibitor versus acetylcholinesterase. For both enzymes, the -log K(i) values linearly correlate with the difference of substituted phenyl radius of cage amines (-log K(i)=5.4+3.4Deltagamma for acetylcholinesterase, -log K(i)=5.9+3.2Deltagamma for butyrylcholinesterase). Moreover, the relationship between the enzymes and cage amines mimics that between bottles and stoppers.
Lin
Gialih
G
Department of Chemistry, National Chung-Hsing University, Taichung, Taiwan. gilin@dragon.nchu.edu.tw
Tsai
Hou-Jen
HJ
Tsai
Yi-Hon
YH
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000838:Anions / Q000737:chemistry; D001596:Benzylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000378:metabolism; D002412:Cations / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004491:Edrophonium / Q000494:pharmacology; D004593:Electrophorus; D006736:Horses; D006868:Hydrolysis; D007700:Kinetics; D013329:Structure-Activity Relationship
D000838:Anions; D001596:Benzylamines; D002412:Cations; D002800:Cholinesterase Inhibitors; D004491:Edrophonium; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase