dc.contributor.author |
Mohamed, Abdelrahman |
|
dc.contributor.author |
Salah, Mohamed |
|
dc.contributor.author |
Tahoun, Mariam |
|
dc.contributor.author |
Hawner, Manuel |
|
dc.contributor.author |
Abdelsamie, Ahmed S |
|
dc.contributor.author |
Frotscher, Martin |
|
dc.date.accessioned |
2022-09-17T07:48:53Z |
|
dc.date.available |
2022-09-17T07:48:53Z |
|
dc.date.issued |
2022 |
|
dc.identifier.other |
https://doi.org/10.1021/acs.jmedchem.2c00589 |
|
dc.identifier.uri |
http://repository.msa.edu.eg/xmlui/handle/123456789/5182 |
|
dc.description.abstract |
A novel approach for the dual inhibition of steroid sulfatase (STS) and 17ß-hydroxysteroid dehydrogenase type 1(17ß HSD1) by a single drug was explored, starting from in-house 17ß 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 17ß-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 17ß-HSD1 inhibition in cell-free and cellular assays, high selectivity over 17ß-HSD2, reasonable metabolic stability, and low estrogen receptor a affinity. A close relationship was found between the liberation of the phenolic compound by sulfamate hydrolysis and 17ß-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. © 2022 American Chemical Society. |
en_US |
dc.description.uri |
https://www.scimagojr.com/journalsearch.php?q=23041&tip=sid&clean=0 |
|
dc.language.iso |
en_US |
en_US |
dc.publisher |
American Chemical Society |
en_US |
dc.relation.ispartofseries |
Journal of Medicinal Chemistry; |
|
dc.subject |
Steroid Sulfatase |
en_US |
dc.subject |
(STS) and 17β-Hydroxysteroid Dehydrogenase Type 1 |
en_US |
dc.subject |
(17β-HSD1) |
en_US |
dc.subject |
Treatment of Endometriosis |
en_US |
dc.title |
Dual Targeting of Steroid Sulfatase (STS) and 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) by a Novel Drug-Prodrug Approach: A Potential Therapeutic Option for the Treatment of Endometriosis |
en_US |
dc.type |
Article |
en_US |
dc.identifier.doi |
https://doi.org/10.1021/acs.jmedchem.2c00589 |
|
dc.Affiliation |
October university for modern sciences and Arts MSA |
|