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Synthesis and Biological Evaluation of 3,5-Diaryl-Substituted 1,2,4-Oxadiazole Sulfamates as Potent Steroid Sulfatase Inhibitors.

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ACS medicinal chemistry letters 📖 저널 OA 100% 2024: 2/2 OA 2025: 12/12 OA 2026: 16/16 OA 2024~2026 2026 Vol.17(2) p. 510-519
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Biernacki K, Ciupak O, Daśko M, Grobelna A, Mirocki A, Rak J

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A novel series of 3,5-disubstituted 1,2,4-oxadiazole sulfamates was synthesized and evaluated as steroid sulfatase (STS) inhibitors.

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APA Biernacki K, Ciupak O, et al. (2026). Synthesis and Biological Evaluation of 3,5-Diaryl-Substituted 1,2,4-Oxadiazole Sulfamates as Potent Steroid Sulfatase Inhibitors.. ACS medicinal chemistry letters, 17(2), 510-519. https://doi.org/10.1021/acsmedchemlett.5c00706
MLA Biernacki K, et al.. "Synthesis and Biological Evaluation of 3,5-Diaryl-Substituted 1,2,4-Oxadiazole Sulfamates as Potent Steroid Sulfatase Inhibitors.." ACS medicinal chemistry letters, vol. 17, no. 2, 2026, pp. 510-519.
PMID 41704353 ↗

Abstract

A novel series of 3,5-disubstituted 1,2,4-oxadiazole sulfamates was synthesized and evaluated as steroid sulfatase (STS) inhibitors. Molecular docking predicted high affinity (binding energies of up to -8.9 kcal·mol), often surpassing the reference Irosustat. Biological evaluation confirmed potent inhibition; compound reduced enzymatic STS activity to 3.5% at 10 μM. In JEG-3 cells, the most potent derivative, , exhibited an IC of 6.64 nM, comparable to that of Irosustat (4.19 nM). Structure-activity relationship analysis revealed that the substitution pattern of the oxadiazole heterocycle plays a decisive role in determining biological activity. Shifting the aryl-sulphamate pharmacophore between positions 3- and 5- of the 1,2,4-oxadiazole heterocycle is crucial for maintaining high biological activity. These findings establish 3,5-disubstituted 1,2,4-oxadiazole sulfamates as promising leads for treating hormone-dependent cancers.

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