Linked Life Data

16279782

Source:http://linkedlifedata.com/resource/pubmed/id/16279782

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2005-11-10
pubmed:abstractText
In this comprehensive study on the caspase-mediated apoptosis-inducing effect of 51 substituted phenols in a murine leukemia cell line (L1210), we determined the concentrations needed to induce caspase activity by 50% (I50) and utilized these data to develop the following quantitative structure-activity relationship (QSAR) model: log 1/I50 = 1.06 B5(2) + 0.33 B5(3) - 0.18pi(2,4) - 0.92. B5(3) and B5(2) represent steric terms, while pi(2,4) represents the hydrophobic character of the substituents on the ring. The strong dependence of caspase-mediated apoptosis on mostly steric parameters suggests that the process is a receptor-mediated interaction with caspases or mitochondrial proteins being the likely targets. Conversely, cytotoxicity studies of 65 electron-releasing phenols in the L1210 cell line led to the development of the following equation: log 1/ID50 = -1.39sigma+ - 0.28 B5(2,6) + 0.16 log P - 0.58I(2) - 1.04I(1) + 3.90. The low coefficient with log P may pertain to cellular transport that may be enhanced by a modest increase in overall hydrophobicity, while the presence of sigma+ is consistent with the suggestion that radical stabilization is of prime importance in the case of electron-releasing substituents. On the other hand, the QSAR for the interactions of 27 electron-attracting phenols in L1210 cells, log 1/ID50 = 0.56 log P - 0.30 B5(2) + 2.79, suggests that hydrophobicity, as represented by log P is of critical importance. Similar cytotoxicity patterns are observed in other mammalian cell lines such as HL-60, MCF-7, CCRF-CEM, and CEM/VLB. The significant differences between the cytotoxicity and apoptosis QSAR for electron-releasing phenols suggest that cytotoxicity involves minimal apoptosis in most of these substituted monophenols.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7234-42
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Cellular apoptosis and cytotoxicity of phenolic compounds: a quantitative structure-activity relationship study.
pubmed:affiliation
Department of Chemistry, Pomona College, 645 North College Avenue, Claremont, California 91711, USA. cselassie@pomona.edu
pubmed:publicationType
Journal Article