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doi:10.22028/D291-43386
Titel: | Dual Targeting of Steroid Sulfatase and 17β-Hydroxysteroid Dehydrogenase Type 1 by a Novel Drug-Prodrug Approach: A Potential Therapeutic Option for the Treatment of Endometriosis |
VerfasserIn: | Mohamed, Abdelrahman Salah, Mohamed Tahoun, Mariam Hawner, Manuel Abdelsamie, Ahmed S. Frotscher, Martin |
Sprache: | Englisch |
Titel: | Journal of Medicinal Chemistry |
Bandnummer: | 65 |
Heft: | 17 |
Seiten: | 11726-11744 |
Verlag/Plattform: | ACS |
Erscheinungsjahr: | 2022 |
DDC-Sachgruppe: | 500 Naturwissenschaften |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | A novel approach for the dual inhibition of steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1(17β HSD1) by a single drug was explored, starting from in-house 17β HSD1 inhibitors via masking their phenolic OH group with a sulfamate ester. The sulfamates were intentionally designed as drugs for the inhibition of STS and, at the same time, prodrugs for 17β-HSD1 inhibition (“drug-prodrug approach”). The most promising sulfamates 13, 16, 18−20, 22−24, 36, and 37 showed nanomolar IC50 values for STS inhibition in a cellular assay and their corresponding phenols displayed potent 17β-HSD1 inhibition in cell-free and cellular assays, high selectivity over 17β-HSD2, reasonable metabolic stability, and low estrogen receptor α affinity. A close relationship was found between the liberation of the phenolic compound by sulfamate hydrolysis and 17β-HSD1 inactivation. These results showed that the envisaged drug-prodrug concept was successfully implemented. The novel compounds constitute a promising class of therapeutics for the treatment of endometriosis and other estrogen-dependent diseases. |
DOI der Erstveröffentlichung: | 10.1021/acs.jmedchem.2c00589 |
URL der Erstveröffentlichung: | https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c00589 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-433864 hdl:20.500.11880/38906 http://dx.doi.org/10.22028/D291-43386 |
ISSN: | 1520-4804 0022-2623 |
Datum des Eintrags: | 7-Nov-2024 |
Bezeichnung des in Beziehung stehenden Objekts: | Supporting Information |
In Beziehung stehendes Objekt: | https://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.2c00589/suppl_file/jm2c00589_si_001.pdf https://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.2c00589/suppl_file/jm2c00589_si_002.csv |
Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Pharmazie |
Professur: | NT - Prof. Dr. Christian Ducho NT - Prof. Dr. Rolf W. Hartmann |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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