ArticleChemMedChem2026
1,2,3-Benzoxathiazine-2,2-Dioxides as Inhibitors of Thioredoxin Reductase.
Article in ChemMedChem, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Thioredoxin reductase 1 (TrxR1) is a selenoenzyme central to cellular redox homeostasis. It is frequently upregulated in cancer and represents an attractive therapeutic target for covalent inhibition. 1,2,3-Benzoxathiazine-2,2-dioxides are bioisosteres of coumarin that have been investigated before as cancer-associated enzyme inhibitors but never as inhibitors of TrxR. In this study, 52 derivatives of 1,2,3-benzoxathiazine-2,2-dioxides were synthesized and evaluated for inhibition of recombinant rat TrxR1 using a DTNB (5,5'-Dithiobis-(2-nitrobenzoic acid)-based colorimetric assay. Although 4-methyl substituted derivatives expressed no activity, the TrxR inhibition effect was observed in the case of 4-unsubstituted 1,2,3-benzoxathiazine-2,2-dioxides, with some derivatives showing micromolar inhibition toward TrxR1. The most potent inhibitors were 8-aryl analogs 7k and 7l with IC
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