| dc.contributor.author |
Zoi, OG |
en |
| dc.contributor.author |
Thireou, TN |
en |
| dc.contributor.author |
Rinotas, VE |
en |
| dc.contributor.author |
Tsoungas, PG |
en |
| dc.contributor.author |
Eliopoulos, EE |
en |
| dc.contributor.author |
Douni, EK |
en |
| dc.contributor.author |
Labrou, NE |
en |
| dc.contributor.author |
Clonis, YD |
en |
| dc.date.accessioned |
2014-06-06T06:52:25Z |
|
| dc.date.available |
2014-06-06T06:52:25Z |
|
| dc.date.issued |
2013 |
en |
| dc.identifier.issn |
10870571 |
en |
| dc.identifier.uri |
http://dx.doi.org/10.1177/1087057113492335 |
en |
| dc.identifier.uri |
http://62.217.125.90/xmlui/handle/123456789/6001 |
|
| dc.subject |
enzyme inhibition |
en |
| dc.subject |
glutathione transferase |
en |
| dc.subject |
multiple drug resistance |
en |
| dc.subject |
xanthone analogue |
en |
| dc.subject.other |
glutathione transferase A1 |
en |
| dc.subject.other |
isoenzyme |
en |
| dc.subject.other |
xanthone derivative |
en |
| dc.subject.other |
article |
en |
| dc.subject.other |
cell lysate |
en |
| dc.subject.other |
colon cancer |
en |
| dc.subject.other |
controlled study |
en |
| dc.subject.other |
drug cytotoxicity |
en |
| dc.subject.other |
drug design |
en |
| dc.subject.other |
drug potency |
en |
| dc.subject.other |
drug screening |
en |
| dc.subject.other |
drug synthesis |
en |
| dc.subject.other |
human |
en |
| dc.subject.other |
human cell |
en |
| dc.subject.other |
IC 50 |
en |
| dc.subject.other |
LC 50 |
en |
| dc.subject.other |
multidrug resistance |
en |
| dc.subject.other |
pharmacophore |
en |
| dc.subject.other |
priority journal |
en |
| dc.subject.other |
structure activity relation |
en |
| dc.subject.other |
enzyme inhibition |
en |
| dc.subject.other |
glutathione transferase |
en |
| dc.subject.other |
multiple drug resistance |
en |
| dc.subject.other |
xanthone analogue |
en |
| dc.subject.other |
Antineoplastic Agents |
en |
| dc.subject.other |
Binding, Competitive |
en |
| dc.subject.other |
Caco-2 Cells |
en |
| dc.subject.other |
Cell Survival |
en |
| dc.subject.other |
Diazonium Compounds |
en |
| dc.subject.other |
Dose-Response Relationship, Drug |
en |
| dc.subject.other |
Drug Resistance, Multiple |
en |
| dc.subject.other |
Drug Resistance, Neoplasm |
en |
| dc.subject.other |
Enzyme Assays |
en |
| dc.subject.other |
Enzyme Inhibitors |
en |
| dc.subject.other |
Glutathione Transferase |
en |
| dc.subject.other |
Humans |
en |
| dc.subject.other |
Isoenzymes |
en |
| dc.subject.other |
Molecular Docking Simulation |
en |
| dc.subject.other |
Recombinant Proteins |
en |
| dc.subject.other |
Structure-Activity Relationship |
en |
| dc.subject.other |
Xanthones |
en |
| dc.title |
Designer xanthone: An inhibitor scaffold for MDR-involved human glutathione transferase isoenzyme A1-1 |
en |
| heal.type |
journalArticle |
en |
| heal.identifier.primary |
10.1177/1087057113492335 |
en |
| heal.publicationDate |
2013 |
en |
| heal.abstract |
Glutathione transferases (GSTs) are cell detoxifiers involved in multiple drug resistance (MDR), hampering the effectiveness of certain anticancer drugs. To our knowledge, this is the first report on well-defined synthetic xanthones as GST inhibitors. Screening 18 xanthones revealed three derivatives bearing a bromomethyl and a methyl group (7) or two bromomethyl groups (8) or an aldehyde group (17), with high inhibition potency (>85%), manifested by low IC50 values (7: 1.59 ± 0.25 μM, 8: 5.30 ± 0.30 μM, and 17: 8.56 ± 0.14 μM) and a competitive modality of inhibition versus CDNB (Ki(7) = 0.76 ± 0.18 and Ki(17) = 1.69 ± 0.08 μM). Of them, derivative 17 readily inhibited hGSTA1-1 in colon cancer cell lysate (IC50 = 10.54 ± 2.41 μM). Furthermore, all three derivatives were cytotoxic to Caco-2 intact cells, with 17 being the least cytotoxic (LC50 = 151.3 ± 16.3 μM). The xanthone scaffold may be regarded as a pharmacophore for hGSTA1-1 and the three derivatives, especially 17, as potent precursors for the synthesis of new inhibitors and conjugate prodrugs for human GSTs. © 2013 Society for Laboratory Automation and Screening. |
en |
| heal.journalName |
Journal of Biomolecular Screening |
en |
| dc.identifier.issue |
9 |
en |
| dc.identifier.volume |
18 |
en |
| dc.identifier.doi |
10.1177/1087057113492335 |
en |
| dc.identifier.spage |
1092 |
en |
| dc.identifier.epage |
1102 |
en |