Linked Life Data

19748786

Source:http://linkedlifedata.com/resource/pubmed/id/19748786

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2009-10-6
pubmed:abstractText
In the present study, we carried out Mannich-type reaction to synthesize clioquinol-derived 7-methyl-arylsulfonylpiperazine analogs with improved growth-inhibitory effects. 11 bearing 5-nitro group on the quinoline ring exhibited 26-fold more potent than that of clioquinol against HeLa cells with a GI(50) value of 0.71 microM. In addition, 11 revealed synergistic effects on the growth inhibition of HeLa cells with GI(50) values of 0.65, 0.25, and 0.06 microM in the presence of 1, 10, and 50 microM copper, respectively. Consistent to the clioquinol-mediated apoptosis, mechanistic study indicates that 9- and 11-induced growth inhibition is attributed to caspase-dependent pathway. Detection of reactive oxygen species in response to clioquinol, 9 and 11 confirmed that ROS was dramatically stimulated in the presence of copper and partially abolished upon treatment of 1mM tempol. Further study indicated that 9- and 11-mediated induction of oxidative stress by ROS generation resulted in the activation MAPK pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1464-3391
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7239-47
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Synthesis and pharmacological exploitation of clioquinol-derived copper-binding apoptosis inducers triggering reactive oxygen species generation and MAPK pathway activation.
pubmed:affiliation
Institute of Clinical Medicine, National Cheng Kung University, Tainan 701, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't