Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines.
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Yu QS, Zhu X, Holloway HW, Whittaker NF, Brossi A, Greig NH
Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines.
J Med Chem. 2002 Aug 15;45(17):3684-91.
- PubMed ID
- 12166941 [ View in PubMed]
- Abstract
A series of phenylcarbamate analogues of geneserine (8, 10, 12, 14) were synthesized from their counterparts, the phenylcarbamate analogues of physostigmine (2-5), by oxidation. The geneserine analogues can undergo tautomerism between N-oxide and 1,2-oxazine structures in a pH- and time-dependent manner. Assessment by (1)H NMR indicated that the N-oxide structure is adopted at neutral pH and that the compound exists in an equilibrium between several epimers. Evaluation of their biological action to inhibit human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), ex vivo, demonstrated that the N-oxide (7, 9, 11, 13, 15) and 1,2-oxazine (6, 8, 10, 12, 14) structures possessed similar potencies against AChE, but the latter structures were more potent against BChE. With the exception of the BChE selective inhibitor, 12, none of the geneserine analogues were as potent or enzyme subtype selective as their physostigmine analogue counterparts.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Donepezil Acetylcholinesterase IC 50 (nM) 22 8 37 Details Galantamine Acetylcholinesterase IC 50 (nM) 800 8 37 Details Huperzine A Acetylcholinesterase IC 50 (nM) 47 8 37 Details Rivastigmine Acetylcholinesterase IC 50 (nM) 4150 8 37 Details Tacrine Acetylcholinesterase IC 50 (nM) 190 8 37 Details