Linked Life Data

16190767

Source:http://linkedlifedata.com/resource/pubmed/id/16190767

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2005-9-29
pubmed:abstractText
The chemoprotection of cells from apoptosis induced by toxins or ionizing radiation could be important for biodefense and in the treatment of acute injuries. We describe a series of small heterocycles, including fused benzothiazoles, benzimidazoles, and related compounds, that abrogate thymocyte apoptosis induced by dexamethasone and gamma-irradiation. To optimize the protective activity of the previously reported pifithrin-alpha (PFT-alpha, 1), various derivatives and analogues of this and the corresponding ring-closed imidazobenzothiazole (IBT, 39) were synthesized. The aromatic analogues of 39 were more protective than 39, while the aromatic analogues of 1 were not active. Compound 19 containing a pyrrolidinyl substituent on the phenyl ring provided potent antiapoptotic activity (EC50 of 1.31 microM compared to 4.16 microM for 1). Modification of aromatic 39 with a pyrrolidinyl para substituent (compound 60) enhanced the activity, lowering the EC50 to 0.35 microM. Also, 60 provided significant protection against gamma-irradiation-induced apoptosis, as expected. Compounds 19 and 60 may be promising for potential clinical development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6409-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Inhibitors of apoptosis in lymphocytes: synthesis and biological evaluation of compounds related to pifithrin-alpha.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0663, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural