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• W2123288529 endingPage "1102" @default.
• W2123288529 startingPage "1092" @default.
• W2123288529 abstract "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." @default.
• W2123288529 created "2016-06-24" @default.
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• W2123288529 date "2013-10-01" @default.
• W2123288529 modified "2023-10-16" @default.
• W2123288529 title "Designer Xanthone: An Inhibitor Scaffold for MDR-Involved Human Glutathione Transferase Isoenzyme A1-1" @default.
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• W2123288529 doi "https://doi.org/10.1177/1087057113492335" @default.
• W2123288529 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23749766" @default.
• W2123288529 hasPublicationYear "2013" @default.
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