1392510-46-1Relevant articles and documents
Synthesis and study of 2-(pyrrolesulfonylmethyl)- N -arylimines: A new class of inhibitors for human glutathione transferase A1-1
Koutsoumpli, Georgia E.,Dimaki, Virginia D.,Thireou, Trias N.,Eliopoulos, Elias E.,Labrou, Nikolaos E.,Varvounis, George I.,Clonis, Yannis D.
, p. 6802 - 6813 (2012/09/25)
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 (Ki(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.
