Linked Life Data

833827

Source:http://linkedlifedata.com/resource/pubmed/id/833827

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1977-3-15
pubmed:abstractText
As a continuation of our efforts to develop and study inhibitors which act presynaptically on neuromuscular function, sulfur analogues of hemicholinium-3 (HC-3, 1) and acetyl-seco-hemicholinium-3 (AcHC-3, 3) were prepared. In each case sulfur is substituted for the noncarbonyl oxygen in HC-3 (1) and AcHC-3 (3). As expected on the basis of conformational differences between acetylcholine and acetylthiocholine both of the thio analogues are produced in the seco form and do not cyclize spontaneously or when subjected to aqueous, acidic conditions up to 100 degrees C. Both compounds are stable in aqueous pH 7.4 solutions at 37 degrees C and in slightly acidic D2O solutions for more than 24 h. While thio-seco-hemicholinium 3 (11) is stable in the presence of acetylcholinesterase and butyrylcholinesterase in H2O at pH 7.4, acetylthio-seco-hemicholinium-3 (12) reacts within seconds to form the hemiacetal form of thiohemicholinium-3 (16). Mouse toxicity studies (LD50) indicate that while 12 is approximately as toxic as HC-3 (1) and AcHC-3 (3), 11 is 226 times less toxic. As in the studies with 1 and 3, mice were protected from 11 by choline and slightly by neostigmine. It is of interest, however, that almost equal and intermediate protection against 12 was afforded by choline and neostigmine. Structure-toxicity relationships of 1,3,11, 12, and 16 are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
59-62
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1977
pubmed:articleTitle
Effect of sulfur substitution for the noncarbonyl oxygen in hemicholinium-3 and acetyl-seco-hemicholinium-3. Synthesis, biological activity, and structure-toxicity relationships.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.