Novel inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) and steroid sulfatase (STS) with unique dual mode of action : potential drugs for the treatment of non-small cell lung cancer (NSCLC) and endometriosis
2023
Hochschulschrift
Zugriff:
Estrogens, in particular estradiol (E2) play an important role in estrogen-dependent diseases (EDDs), such as non-small-cell lung cancer (NSCLC) and endometriosis. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is frequently expressed in NSCLC tissues, leading to cancer development and progression. Thus, the first objective of this study (chapter 3.1) is the development of a novel series of highly potent non-steroidal, selective 17β-HSD1 inhibitors in order to enhance the treatment of NSCLC. This section of the study showed that 17β-HSD1 is a promising therapeutic target for NSCLC, providing new avenues for the treatment of this lethal cancer. Steroid sulfatase (STS) and 17β-HSD1 are promising targets for the treatment of endometriosis because they limit estrogen formation mainly in the target cells, leading to fewer side effects. Thus, the second part of the study (chapter 3.2) aims at developing dual inhibitors of STS and 17β-HSD1, which provide a novel treatment option. The synthesized sulfamates should be drugs for inhibition of STS, and prodrugs for 17β-HSD1 inhibition. The most active compounds of this part showed nanomolar IC50 values for STS in cellular assays and their corresponding phenols displayed potent 17β-HSD1 inhibition in cell-free and cellular assays as well as high selectivity over 17β-HSD2. These findings suggest that the “drug-prodrug concept” has been applied successfully (chapter 3.2).
Titel: |
Novel inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) and steroid sulfatase (STS) with unique dual mode of action : potential drugs for the treatment of non-small cell lung cancer (NSCLC) and endometriosis
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Autor/in / Beteiligte Person: | Mohamed, Abdelrahman Mohamed Mahmoud |
Link: | |
Veröffentlichung: | 2023 |
Medientyp: | Hochschulschrift |
DOI: | 10.22028/D291-39318 |
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