Linked Life Data

19827033

Source:http://linkedlifedata.com/resource/pubmed/id/19827033

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-10-19
pubmed:abstractText
We have reported that benzene-1,2-, 1,3-, and 1,4-di-N-substituted carbamates (1-15) are characterized as the conformationally constrained inhibitors of acetylcholinesterase and mimic gauche, eclipsed, and anti-conformations of acetylcholine, respectively (J Biochem Mol Toxicol 2007;21:348-353). We further report the inhibition of butyrylcholinesterase by these inhibitors. Carbamates 1-15 are also characterized as the pseudosubstrate inhibitors of butyrylcholinesterase as in the acetylcholinesterase catalysis. Benzene-1,4-di-N-n-hexylcarbamate (12) and benzene-1,4-di-N-n-octylcarbamate (13) are the two most potent inhibitors of butyrylcholinesterase among inhibitors 1-15. These two para compounds, with the angle of 180 degrees between two C(benzene)--O bonds, mimic the preferable anti C--O/C--N conformers for the choline ethylene backbone of butyrylcholine during the butyrylcholinesterase catalysis. The second n-hexylcarbamyl or n-octylcarbamyl moiety of inhibitors 12 and 13 is proposed to bind tightly to the peripheral anionic site of butyrylcholinesterase from molecular modeling. Butyrylcholinesterase prefers para-carbamates to ortho- and meta-carbamates, whereas acetylcholinesterase prefers para- and meta-carbamates to ortho-carbamates. This result implies that the anionic site of butyrylcholinesterase is relatively smaller than that of acetylcholinesterase because meta-carbamates, which may bind to the anionic sites of both enzymes, are not potent inhibitors of butyrylcholinesterase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1099-0461
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
303-8
pubmed:dateRevised
2011-3-18
pubmed:meshHeading
pubmed:articleTitle
Comparison of active sites of butyrylcholinesterase and acetylcholinesterase based on inhibition by geometric isomers of benzene-di-N-substituted carbamates.
pubmed:affiliation
Department of Neurosurgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't