C-3 Steroidal Hemiesters as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 10

0584443 - ÚOCHB 2025 RIV US eng J - Článek v odborném periodiku
Hanzlová, M. - Slavíková, Barbora - Morozovová, Marina - Musílek, K. - Rotterová, A. - Zemanová, L. - Kudová, Eva
C-3 Steroidal Hemiesters as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 10.
ACS Omega. Roč. 9, č. 10 (2024), s. 12116-12124. ISSN 2470-1343. E-ISSN 2470-1343
Institucionální podpora: RVO:61388963
Klíčová slova: alzheimers-disease * design * roles
Impakt faktor: 4.1, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1021/acsomega.3c10148

17 beta-HSD10 is a mitochondrial enzyme that catalyzes the steroidal oxidation of a hydroxy group to a keto group and, thus, is involved in maintaining steroid homeostasis. The druggability of 17 beta-HSD10 is related to potential treatment for neurodegenerative diseases, for example, Alzheimer's disease or cancer. Herein, steroidal derivatives with an acidic hemiester substituent at position C-3 on the skeleton were designed, synthesized, and evaluated by using pure recombinant 17 beta-HSD10 converting 17 beta-estradiol to estrone. Compounds bold22/bold (IC50 = 6.95 +/- 0.35 mu M) and bold23/bold (IC50 = 5.59 +/- 0.25 mu M) were identified as the most potent inhibitors from the series. Compound bold23/bold inhibited 17 beta-HSD10 activity regardless of the substrate. It was found not cytotoxic toward the HEK-293 cell line and able to inhibit 17 beta-HSD10 activity also in the cellular environment. Together, these findings support steroidal compounds as promising candidates for further development as 17 beta-HSD10 inhibitors.
Trvalý link: https://hdl.handle.net/11104/0352357