Linked Life Data

1954229

Source:http://linkedlifedata.com/resource/pubmed/id/1954229

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1991-12-30
pubmed:abstractText
Halogeno benzimidazole and benzimidazole nucleoside analogues have been screened for inhibitory activity vs. purified plant (maize seedling) casein kinases I, IIA and IIB, and the results compared with those previously reported for some of the compounds as inhibitors of the corresponding mammalian CK-1 and CK-2 (Meggio et al. (1990) Eur. J. Biochem. 187, 89-94). One new analogue, the riboside of 5,7-dibromobenzimidazole, which is sterically constrained to the anti conformation about the glycosidic bond, and is a good inhibitor, exhibited appreciable (5-7-fold) discrimination between the type I and type II enzymes. An increase in the number of halogen substituents on the benzene ring of benzimidazole from two to three led to marked enhancement of inhibitory activity, particularly against the type II enzymes, with a decrease in Ki from 24 to 4 microM. The 2-aza analogue of 5,6-dichlorobenzimidazole, i.e. 5,6-dichlorobenzotriazole, as the free base, even more effectively discriminated between the two types of plant casein kinases, with Ki approximately 100 microM for CK-I, and Ki approximately 9 microM for CK-IIA and CK-IIB. Inhibition in all instances was competitive with respect to ATP (for CK-I), and ATP and GTP (for CK-IIA and CK-IIB). The results are compared with those for halogenated isoquinolinesulfonamide inhibitors reported by Chijiwa et al. (J. Biol. Chem. (1989) 264, 4924-4927), leading to proposals for the synthesis of potentially more effective and more discriminating inhibitors. Attention is drawn to the significant role of the halogen substituents in the mechanism(s) of action of the structurally related benzimidazole, benzotriazole and naphthalene and isoquinoline, inhibitors of protein kinases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
1080
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Benzimidazole nucleoside analogues as inhibitors of plant (maize seedling) casein kinases.
pubmed:affiliation
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't