Linked Life Data

21115210

Source:http://linkedlifedata.com/resource/pubmed/id/21115210

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-21
pubmed:abstractText
The study described here concerns the synthesis of a series of thirty new symmetrically substituted imidothiocarbamate and imidoselenocarbamate derivatives and their evaluation for antitumoral activity in vitro against a panel of five human tumor cell lines: breast adenocarcinoma (MCF-7), colon carcinoma (HT-29), lymphocytic leukemia (K-562), hepatocarcinoma (Hep-G2), prostate cancer (PC-3) and one non-malignant mammary gland-derived cell line (MCF-10A). The GI(50) values for eighteen of the compounds were below 10 ?M in at least one cell line. Two cancer cells (MCF-7 and HT-29) proved to be the most sensitive to five compounds (1b, 2b, 3b, 4b and 5b), with growth inhibition in the nanomolar range, and compounds 1b, 3b, 7b, 8b and 9b gave values of less than 1 ?M. In addition, all of the aforementioned compounds exhibited lower GI(50) values than some of the standard chemotherapeutic drugs used as references. The results also reveal that the nature of the aliphatic chain (methyl is better than benzyl) at the selenium position and the nature of the heteroatom (Se better than S) have a marked influence on the antiproliferative activity of the compounds. These findings reinforce our earlier hypothesis concerning the determinant role of the selenomethyl group as a scaffold for the biological activity of this type of compound. Considering both the cytotoxic parameters and the selectivity index (which was compared in MCF-7 and MCF-10A cells), compounds 2b and 8b (with a selenomethyl moiety) displayed the best profiles, with GI(50) values ranging from 0.34 nM to 6.07 ?M in the five cell lines tested. Therefore, compounds 2b and 8b were evaluated by flow cytometric analysis for their effects on cell cycle distribution and apoptosis in MCF-7 cells. 2b was the most active, with an apoptogenic effect similar to camptothecin, which was used as a positive control. Both of them provoked cell cycle arrest leading to the accumulation of cells in either G(2)/M and S phase. These two compounds can therefore be considered as the most promising candidates for the development of novel generations of antitumor agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1768-3254
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
265-74
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Synthesis and antiproliferative activity of novel symmetrical alkylthio- and alkylseleno-imidocarbamates.
pubmed:affiliation
Synthesis Section, Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't