eng URI http://hdl.handle.net/10795/2643 βιοχημεία ένζυμο φαρμακευτική The selectivity of certain benzophenones and their carbonyl N-analogues was investigated towards the human GSTP1-1 allozymes A, B and C involved in MDR. The allozymes were purified from extracts derived from E. coli harbouring the plasmids pEXP5-CT/TOPO-TAhGSTP1* A, pOXO4-hGSTP1*B or pOXO4-hGSTP1*C. Compound screening with each allozyme activity indicated three compounds with appreciable inhibitory potencies, 12 and 13 with P1-1A 62% and 67%, 11 and 12 with P1-1C 51% and 70%, whereas that of 15 fell behind with P1-1B (41%). These findings were confirmed by IC50 values (74–125 lM). Enzyme inhibition kinetics, aided by molecular modelling and docking, revealed that there is competition with the substrate CDNB for the same binding site on the allozyme (Ki(13/ A) = 63.6 +- 3.0 lM, K (15/B) = 198.6 +- 14.3 lM, and Ki(11/ C) = 16.5 +- 2.7 lM). These data were brought into context by an in silico structural comparative analysis of the targeted proteins. Although the screened compounds showed moderate inhibitory potency against hGSTP1-1, remarkably, some of them demonstrated absolute isoenzyme and/or allozyme selectivity. 9 pp. LOMv1.0 creator LOMv1.0 publisher LOMv1.0 Project Final Beneficiary LOMv1.0 Project Executing Organisation 2015-04-03 Digital Library of the Operational Programme "Education and Lifelong Learning" abstract types Text Allozyme Benzophenone Enzyme cloning Enzyme inhibition Enzyme kinetics Human glutathione transferase Isoenzyme Ketoxime N-acyl hydrazone, Protein structure comparative analysis http://onlinelibrary.wiley.com/doi/10.1111/cbdd.12574/suppinfo 1662440 application/pdf http://repository.edulll.gr/edulll/bitstream/10795/2643/2/2643_Paper%2013.pdf URI http://hdl.handle.net/10795/2643 LOMv1.0creator 2016-04-14T08:08:10Z LOMv1.0validator 2016-04-14T08:08:10Z LOMv1.0 gre no no Copyright EYD-EPEDBM (Operational Programme "Education and Lifelong Learning")