eng URI http://hdl.handle.net/10795/2667 φαρμακευτικό προϊόν ένζυμο βιοχημεία βιοτεχνολογία Glutathione transferases (GSTs) are cell detoxifiers involved in multiple drug resistance (MDR), hampering the effectiveness of certain anticancer drugs. To our knowledge, this is the first report on well-defined synthetic xanthones as GST inhibitors. Screening 18 xanthones revealed three derivatives bearing a bromomethyl and a methyl group (7) or two bromomethyl groups (8) or an aldehyde group (17), with high inhibition potency (>85%), manifested by low IC50 values (7: 1.59 ± 0.25 μM, 8: 5.30 ± 0.30 μM, and 17: 8.56 ± 0.14 μM) and a competitive modality of inhibition versus CDNB (Ki(7) = 0.76 ± 0.18 and Ki(17) = 1.69 ± 0.08 μM). Of them, derivative 17 readily inhibited hGSTA1-1 in colon cancer cell lysate (IC50 = 10.54 ± 2.41 μM). Furthermore, all three derivatives were cytotoxic to Caco-2 intact cells, with 17 being the least cytotoxic (LC50 = 151.3 ± 16.3 μM). The xanthone scaffold may be regarded as a pharmacophore for hGSTA1-1 and the three derivatives, especially 17, as potent precursors for the synthesis of new inhibitors and conjugate prodrugs for human GSTs. 12 pp. LOMv1.0 creator LOMv1.0 publisher LOMv1.0 Project Final Beneficiary LOMv1.0 Project Executing Organisation 2013-06-07 Digital Library of the Operational Programme "Education and Lifelong Learning" abstract types Text Glutathione transferases Multiple drug resistance Cellular detoxification Xanthones Inhibitors Anticancer drugs GTs http://jbx.sagepub.com/content/18/9/1092 1189823 application/pdf http://repository.edulll.gr/edulll/bitstream/10795/2667/2/2667_Paper%205.pdf URI http://hdl.handle.net/10795/2667 LOMv1.0creator 2016-04-15T07:57:26Z LOMv1.0validator 2016-04-15T07:57:26Z LOMv1.0 gre no no Copyright EYD-EPEDBM (Operational Programme "Education and Lifelong Learning")