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Updated: Feb 19, 2026

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Synthesis and Biological Evaluation of 3,5-Diaryl-Substituted 1,2,4-Oxadiazole Sulfamates as Potent Steroid Sulfatase
Karol Biernacki1, Olga Ciupak2, Mateusz Daśko2
1Department of Organic Chemistry, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12 Street, 80-233 Gdańsk, Poland.
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-1), often surpassing the reference Irosustat. Biological evaluation confirmed potent inhibition; compound 9n reduced enzymatic STS activity to 3.5% at 10 μM. In JEG-3 cells, the most potent derivative, 9j, exhibited an IC50 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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