Linked Life Data

20933308

Source:http://linkedlifedata.com/resource/pubmed/id/20933308

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-11-24
pubmed:abstractText
The biological importance of microtubules in mitosis, as well as in interphase, makes them an interesting target for the development of anticancer agents. Small molecules such as benzo[b]thiophenes are attractive as inhibitors of tubulin polymerization. Thus, a new class of compounds that incorporated the structural motif of the 2-(3',4',5'-trimethoxybenzoyl)-3-aryl/arylamino benzo[b]thiophene molecular skeleton, with electron-donating (Me, OMe, SMe or OEt) or electron-withdrawing (F and Cl) substituents on the B-ring, was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization and cell cycle effects. The most promising compound in this series was 2-(3',4',5'-trimethoxybenzoyl)-3-(4'-ethoxyphenyl)-benzo[b]thiophene (4e), which significantly inhibited cancer cell growth at submicromolar concentrations, especially against HeLa and Jurkat cells, and interacted with tubulin. As determined by flow cytometric analysis, 4e caused G2/M phase arrest and apoptosis in a time- and concentration-dependent manner. The block in G2/M was correlated with increased expression of cyclin B1 and phosphorylation of cdc25c. Moreover, 4e perturbed mitochondrial membrane potential and caused activation of caspase-3 and cleavage of poly(ADP-rybose)polymerase (PARP), events that are involved in 4e-induced apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
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
5781-91
pubmed:dateRevised
2011-4-13
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-aryl/arylaminobenzo[b]thiophene derivatives as a novel class of antiproliferative agents.
pubmed:affiliation
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy. rmr@unife.it
pubmed:publicationType
Journal Article