| dc.contributor.author |
Koutsoumpli, GE |
en |
| dc.contributor.author |
Dimaki, VD |
en |
| dc.contributor.author |
Thireou, TN |
en |
| dc.contributor.author |
Eliopoulos, EE |
en |
| dc.contributor.author |
Labrou, NE |
en |
| dc.contributor.author |
Varvounis, GI |
en |
| dc.contributor.author |
Clonis, YD |
en |
| dc.date.accessioned |
2014-06-06T06:52:07Z |
|
| dc.date.available |
2014-06-06T06:52:07Z |
|
| dc.date.issued |
2012 |
en |
| dc.identifier.issn |
00222623 |
en |
| dc.identifier.uri |
http://dx.doi.org/10.1021/jm300385f |
en |
| dc.identifier.uri |
http://62.217.125.90/xmlui/handle/123456789/5854 |
|
| dc.subject.other |
1 methyl 2(2 nitrobenzylsulfanyl) 1h pyrrole |
en |
| dc.subject.other |
1 methyl 2[(2 nitrobenzyl) sulfanyl] 1h pyrrole |
en |
| dc.subject.other |
1 methyl 2[(2 nitrobenzyl) sulfonyl)] 1h pyrrole |
en |
| dc.subject.other |
2 (pyrrolesulfonylmethyl) n arylimine |
en |
| dc.subject.other |
2[(1 methyl 1h pyrrol 2 ylsulfonyl) methyl] aniline |
en |
| dc.subject.other |
2[[(1 methyl 1h pyrrol 2 yl) sulfonyl] methyl] n ((1e) (4 nitrophenyl) methylene) aniline |
en |
| dc.subject.other |
2[[(1 methyl 1h pyrrol 2 yl) sulfonyl] methyl] n ((1e) (phenyl) methylene) aniline |
en |
| dc.subject.other |
2[[(1 methyl 1h pyrrol 2 yl) sulfonyl] methyl] n (1e) [4 (trifluoromethyl) phenyl] methylene aniline |
en |
| dc.subject.other |
enzyme inhibitor |
en |
| dc.subject.other |
glutathione transferase A1 |
en |
| dc.subject.other |
imine |
en |
| dc.subject.other |
n ((1e) (4 (dimethylamino) phenyl) methylene) 2[[(1 methyl 1h pyrrol 2 yl) sulfonyl] methyl] aniline |
en |
| dc.subject.other |
n ((1e) (4 fluorophenyl) methylene) 2[[(1 methyl 1h pyrrol 2 yl) sulfonyl] methyl] aniline |
en |
| dc.subject.other |
n ((1e) (5 bromo 2 methoxyphenyl) methylene) 2 [[(1 methyl 1h pyrrol 2 yl) sulfonyl] methyl] aniline |
en |
| dc.subject.other |
pyrrole derivative |
en |
| dc.subject.other |
unclassified drug |
en |
| dc.subject.other |
article |
en |
| dc.subject.other |
competitive inhibition |
en |
| dc.subject.other |
controlled study |
en |
| dc.subject.other |
drug binding |
en |
| dc.subject.other |
drug structure |
en |
| dc.subject.other |
drug synthesis |
en |
| dc.subject.other |
enzyme active site |
en |
| dc.subject.other |
enzyme inhibition |
en |
| dc.subject.other |
molecular model |
en |
| dc.subject.other |
nonhuman |
en |
| dc.subject.other |
Aniline Compounds |
en |
| dc.subject.other |
Enzyme Assays |
en |
| dc.subject.other |
Glutathione Transferase |
en |
| dc.subject.other |
Humans |
en |
| dc.subject.other |
Imines |
en |
| dc.subject.other |
Isoenzymes |
en |
| dc.subject.other |
Kinetics |
en |
| dc.subject.other |
Models, Molecular |
en |
| dc.subject.other |
Protein Binding |
en |
| dc.subject.other |
Pyrroles |
en |
| dc.subject.other |
Recombinant Proteins |
en |
| dc.subject.other |
Stereoisomerism |
en |
| dc.subject.other |
Structure-Activity Relationship |
en |
| dc.subject.other |
Sulfones |
en |
| dc.title |
Synthesis and study of 2-(pyrrolesulfonylmethyl)- N -arylimines: A new class of inhibitors for human glutathione transferase A1-1 |
en |
| heal.type |
journalArticle |
en |
| heal.identifier.primary |
10.1021/jm300385f |
en |
| heal.publicationDate |
2012 |
en |
| heal.abstract |
Overexpression of human GSTA1-1 in tumor cells is part of MDR mechanisms. We report on the synthesis of 11 pyrrole derivatives as hGSTA1-1 inhibitors starting from 1-methyl-2-[(2-nitrobenzylsulfanyl]-1H-pyrrole. Molecular modeling revealed two locations in the enzyme H binding site: the catalytic primary one accommodating shorter and longer derivatives and the secondary one, where shorter derivatives can occupy. Derivative 9, displaying the highest inhibition and bearing a p-nitroarylimino moiety, and derivative 4, lacking this moiety, were studied kinetically. Derivative 9 binds (K i(9) = 71 ± 4 μM) at the primary site competitively vs CDNB. Derivative 4 binds (K i(4) = 135 ± 27 μM) at the primary and secondary sites, allowing the binding of a second molecule (4 or CDNB) leading to formation of unreactive and reactive complexes, respectively. The arylmethylsulfonylpyrrole core structure is a new pharmacophore for hGSTA1-1, whereas its derivative 9 may serve as a lead structure. © 2012 American Chemical Society. |
en |
| heal.journalName |
Journal of Medicinal Chemistry |
en |
| dc.identifier.issue |
15 |
en |
| dc.identifier.volume |
55 |
en |
| dc.identifier.doi |
10.1021/jm300385f |
en |
| dc.identifier.spage |
6802 |
en |
| dc.identifier.epage |
6813 |
en |