Linked Life Data

20843586

Source:http://linkedlifedata.com/resource/pubmed/id/20843586

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-10-11
pubmed:abstractText
A rigorous QSAR modeling procedure employing CODESSA PRO descriptors has been utilized for the prediction of more efficient anti-leukemia agents. Experimental data concerning the effect on leukemia RPMI-8226 cell line tumor growth of 34 compounds (treated at a dose of 10 ?M) was related to their chemical structures by a 4-descriptor QSAR model. Four bis(oxy)bis-urea and bis(sulfanediyl)bis-urea derivatives (4a, 4b, 8, 11a) predicted as active by this model, together with 11b predicted to be of low activity, were synthesized and screened for anti-tumor activity utilizing 55 different tumor cell lines. Compounds 8 and 11a showed anti-tumor properties against most of the adopted cell lines with growth inhibition exceeding 50%. The highly promising preliminary anti-tumor properties of compounds 8 and 11a, were screened at serial dilutions (10(-4)-10(-8) ?M) for determination of their GI(50) and TGI against the screened human tumor cell lines. Compound 11a (GI(50) = 1.55, TGI = 8.68 ?M) is more effective than compound 8 (GI(50)=58.30, TGI = > 100 ?M) against the target leukemia RPMI-8226 cell line. Compound 11a also exhibits highly pronounced anti-tumor properties against NCI-H226, NCI-H23 (non-small cell lung cancer), COLO 205 (colon cancer), SNB-75 (CNS cancer), OVCAR-3, SK-OV-3 (ovarian cancer), A498 (renal cancer) MDA-MB-231/ATCC and MDA-MB-468 (breast cancer) cell lines (GI(50) = 1.95, 1.61, 1.38, 1.56, 1.30, 1.98, 1.18, 1.85, 1.08, TGI = 8.35, 6.01, 2.67, 8.59, 4.01, 7.01, 5.62, 6.38, 5.63 ?M, respectively). Thus 11a could be a suitable lead towards the design of broad spectrum anti-tumor active agents targeting various human tumor cell lines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1768-3254
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5183-99
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
QSAR modeling, synthesis and bioassay of diverse leukemia RPMI-8226 cell line active agents.
pubmed:affiliation
Center for Heterocyclic Compounds, University of Florida, Department of Chemistry, Gainesville, FL 32611-7200, United States. katritzky@chem.ufl.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't