Linked Life Data

18473911

Source:http://linkedlifedata.com/resource/pubmed/id/18473911

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-5-13
pubmed:abstractText
A series of quinoxalines variously substituted, namely 3-arylthiomethyl-1,6-dimethylquinoxalin-2-ones (6a-f), 3-arylthiomethyl-1-benzyl-7-trifluoromethylquinoxalin-2-ones (8a-g) and 2-arylthiomethyl-3-benzyloxy-6-trifluoro-methylquinoxalines (10a,b,e-h), were synthesized and compared with previous arylphenoxymethylquinoxalines (1a-f, 2a-f and 3a-b). The purpose was to verify whether the replacement of oxygen with sulphur atom and the insertion of different substituents on the phenyl side chain were able to improve the capability to inhibit the Pgp pump and restore the antiproliferative activity of clinically useful drugs, such as doxorubicin (Doxo), vincristine (VCR) and etoposide (VP16), in drug-resistant human nasopharyngeal carcinoma KB cells (KB(wt), KB(MDR), KB(7D) and KB(V20C)). Furthermore, 2,3-bis(aryloxy-methyl)-6-trifluoromethylquinoxalines (13a-c) were designed with the objective to evaluate the capability of the double side chain to potentiate the antiproliferative activity of the drugs tested. Biological assays showed that title compounds were, in general, endowed with good activity as Pgp inhibitors. In particular compound 3a, bearing 2-CONHPh substituent on phenoxymethyl side chain, resulted the most effective, while the double side chain (compound 13c) gives the ability to inhibit a different MRP pump (a membrane glycoprotein named mrp). Furthermore, we can conclude that replacement of oxygen with sulphur atom did not improve the biological activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1573-4064
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
194-205
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
2(3)-Aryl-thio(oxy)-methylquinoxaline derivatives: a new class of P-glycoprotein-mediated drug efflux inhibitors.
pubmed:affiliation
Dipartimento Farmaco Chimico Tossicologico, via Muroni 23/a, 07100 Sassari, Italy. acarta@uniss.it
pubmed:publicationType
Journal Article