eng URI http://hdl.handle.net/10795/2652 βιοχημεία ένζυμο 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 (Ki(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. 12 pp. LOMv1.0 creator LOMv1.0 publisher LOMv1.0 Project Final Beneficiary LOMv1.0 Project Executing Organisation 2012-07-31 Digital Library of the Operational Programme "Education and Lifelong Learning" abstract types Text MDR Glutathione transferases Isoenzymes Molecular modeling Human GSTA1-1 in tumor cells http://pubs.acs.org/doi/abs/10.1021/jm300385f 3193628 application/pdf http://repository.edulll.gr/edulll/bitstream/10795/2652/2/2652_Paper%203.pdf URI http://hdl.handle.net/10795/2652 LOMv1.0creator 2016-04-14T09:08:06Z LOMv1.0validator 2016-04-14T09:08:06Z LOMv1.0 gre no no Copyright EYD-EPEDBM (Operational Programme "Education and Lifelong Learning")