Linked Life Data

8135875

Source:http://linkedlifedata.com/resource/pubmed/id/8135875

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-4-18
pubmed:abstractText
A series of newly synthesized 1,5-benzothiazepines derived from diltiazem (CAS 42399-41-7) were tested for calmodulin antagonistic activities using Ca(2+)-calmodulin stimulated phosphodiesterase (PDE). Some compounds possessing the benzoyloxy moieties at position 4 of 1,5-benzothiazepine ring of diltiazem showed a dose-dependent inhibitory action with the potencies comparable to that of a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7). In contrast, diltiazem did not exert the inhibitory action at the same concentrations. Further, radioligand binding experiment, using a radiolabeled 1,5-benzothiazepine, showed that these compounds bound to Ca(2+)-calmodulin complex, but not to calmodulin in the presence of EGTA, suggesting that these 1,5-benzothiazepines are new calmodulin antagonists. Some of these compounds inhibited [3H]diltiazem binding to Ca antagonist binding sites in cell membranes of rat cerebral cortex but with a less potent affinities than diltiazem, suggesting that there was no correlation between their anti-calmodulin effect and the binding affinity to Ca antagonist binding sites. In conclusion, new 1,5-benzothiazepines have been demonstrated to have an anti-calmodulin action. These compounds may possess a pharmacological activity based on their anti-calmodulin action in addition to their interaction with Ca channel.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0004-4172
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3-6
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Calmodulin antagonistic action of new 1,5-benzothiazepines derived from diltiazem.
pubmed:affiliation
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
pubmed:publicationType
Journal Article, In Vitro