biostudies-literatureCirillo DDepartment of Biomedicine at the University of BergenEuropean Commission2650-2668https://www.ebi.ac.uk/biostudies/studies/S-EPMC8518981biostudies-literatureUnknown16(17)The xCT antiporter is a cell membrane protein involved in active counter-transportation of glutamate (outflux) with cystine (influx) over the human cell membrane. This feature makes the xCT antiporter a crucial element of the biosynthesis of the vital free radical scavenger glutathione. The prodrug sulfasalazine, a medication for the treatment of ulcerative colitis, was previously proven to inhibit the xCT antiporter. Starting from sulfasalazine, a molecular scaffold jumping followed by SAR-assisted design and synthesis provided a series of styryl hydroxy-benzoic acid analogues that were biologically tested in vitro for their ability to decrease intracellular glutathione levels using four different cancer cell lines: A172 (glioma), A375 (melanoma), U87 (glioma) and MCF7 (breast carcinoma).ChemMedChemStructure-Activity-Relationship-Aided Design and Synthesis of xCT Antiporter Inhibitors.PMC8518981675417Oyvind Enger PBjorsvik HRCirillo DSarowar SfalseStructure-Activity-Relationship-Aided Design and Synthesis of xCT Antiporter Inhibitors.The xCT antiporter is a cell membrane protein involved in active counter-transportation of glutamate (outflux) with cystine (influx) over the human cell membrane. This feature makes the xCT antiporter a crucial element of the biosynthesis of the vital free radical scavenger glutathione. The prodrug sulfasalazine, a medication for the treatment of ulcerative colitis, was previously proven to inhibit the xCT antiporter. Starting from sulfasalazine, a molecular scaffold jumping followed by SAR-assisted design and synthesis provided a series of styryl hydroxy-benzoic acid analogues that were biologically tested in vitro for their ability to decrease intracellular glutathione levels using four different cancer cell lines: A172 (glioma), A375 (melanoma), U87 (glioma) and MCF7 (breast carcinoma).2021-01-01T00:00:00Z2021 Sep2025-04-04T09:18:39.242Z2025-04-04T09:18:39.242ZS-EPMC85189813384704410.1002/cmdc.202100204