Inhibition of acetylcholinesterase from electric eel by (-)-and (+)-physostigmine and related compounds.
Unnatural (+)-physostigmine (2) inhibited acetylcholinesterase (AChE) from electric eel considerably less than natural (-)-physostigmine (1), but 2 may because of its possible lower toxicity still be an interesting anticholinesterase agent. (-)-Eseroline (3), a major metabolite of (-)-physostigmine (1) and a potent narcotic analgetic, and its unnatural (+)-antipode (4), were both poor inhibitors of the enzyme. (-)-Dihydrosecophysostigmine (5), a ring-open analog of (-)-physostigmine was less, but (-)-N-methylphysostigmine (6) much more potent than the natural alkaloid. The availability of compounds related to (-)- and (+)-physostigmine by improved chemical synthesis suggests that further structural variation may well lead to other biologically interesting AChE inhibitors.
Brossi
A
A
Schönenberger
B
B
Clark
O E
OE
Ray
R
R
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004524:Eels / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D007211:Indoles; D010830:Physostigmine; D000110:Acetylcholinesterase; C022594:eseroline