Synthesis and Study of 2-(Pyrrolesulfonylmethyl)-N-arylimines: A New Class of Inhibitors for Human Glutathione Transferase A1-1

 
This item is provided by the institution :
University of Ioannina
Repository :
Repository of UOI Olympias
see the original item page
in the repository's web site and access all digital files if the item*
share



2012 (EN)
Synthesis and Study of 2-(Pyrrolesulfonylmethyl)-N-arylimines: A New Class of Inhibitors for Human Glutathione Transferase A1-1 (EN)

Koutsoumpli, G. E. (EN)

Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας (EL)
Koutsoumpli, G. E. (EN)

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 mu M) at the primary site competitively vs CDNB. Derivative 4 binds (K-i(4) = 135 +/- 27 mu m) 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. (EN)

hiv-1 reverse-transcriptase (EN)

Πανεπιστήμιο Ιωαννίνων (EL)
University of Ioannina (EN)

J Med Chem (EN)

English

2012

<Go to ISI>://000307264100013

American Chemical Society (EN)



*Institutions are responsible for keeping their URLs functional (digital file, item page in repository site)