Source:http://linkedlifedata.com/resource/pubmed/id/18257542
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2008-3-6
|
| pubmed:abstractText |
Ten cytoselective compounds have been identified from 372 thiazolidinone analogues by applying iterative library approaches. These compounds selectively killed both non-small cell lung cancer cell line H460 and its paclitaxel-resistant variant H460 taxR at an IC 50 between 0.21 and 2.93 microM while showing much less toxicity to normal human fibroblasts at concentrations up to 195 microM. Structure-activity relationship studies revealed that (1) the nitrogen atom on the 4-thiazolidinone ring (ring B in Figure 1) cannot be substituted, (2) several substitutions on ring A are tolerated at various positions, and (3) the substitution on ring C is restricted to the -NMe 2 group at the 4-position. A pharmacophore derived from active molecules suggested that two hydrogen bond acceptors and three hydrophobic regions were common features. Activities against P-gp-overexpressing and paclitaxel-resistant cell line H460 taxR and modeling using a previously validated P-gp substrate pharmacophore suggested that active compounds were not likely P-gp substrates.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0022-2623
|
| pubmed:author |
pubmed-author:EkinsSeanS,
pubmed-author:FangBingliangB,
pubmed-author:LiRongshiR,
pubmed-author:LiuAifengA,
pubmed-author:SunYingY,
pubmed-author:SwaanPeter WPW,
pubmed-author:WuShuhongS,
pubmed-author:YanBingB,
pubmed-author:ZhaiShumeiS,
pubmed-author:ZhangBinB,
pubmed-author:ZhangYingY,
pubmed-author:ZhouHongyuH
|
| pubmed:issnType |
Print
|
| pubmed:day |
13
|
| pubmed:volume |
51
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1242-51
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:18257542-Antineoplastic Agents,
pubmed-meshheading:18257542-Cell Line, Tumor,
pubmed-meshheading:18257542-Cell Proliferation,
pubmed-meshheading:18257542-Combinatorial Chemistry Techniques,
pubmed-meshheading:18257542-Drug Design,
pubmed-meshheading:18257542-Drug Resistance, Neoplasm,
pubmed-meshheading:18257542-Drug Screening Assays, Antitumor,
pubmed-meshheading:18257542-Humans,
pubmed-meshheading:18257542-Hydrogen Bonding,
pubmed-meshheading:18257542-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:18257542-Lung Neoplasms,
pubmed-meshheading:18257542-Models, Molecular,
pubmed-meshheading:18257542-P-Glycoprotein,
pubmed-meshheading:18257542-Paclitaxel,
pubmed-meshheading:18257542-Structure-Activity Relationship,
pubmed-meshheading:18257542-Thiazolidinediones
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells.
|
| pubmed:affiliation |
Department of Chemical Biology and Therapeutics, St. Jude Research Hospital, Memphis, Tennessee 38105, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|