C-3 Steroidal Hemiesters as Inhibitors of 17ß-Hydroxysteroid Dehydrogenase Type 10.
ACS Omega
; 9(10): 12116-12124, 2024 Mar 12.
Article
in En
| MEDLINE
| ID: mdl-38496976
ABSTRACT
17ß-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 17ß-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 17ß-HSD10 converting 17ß-estradiol to estrone. Compounds 22 (IC50 = 6.95 ± 0.35 µM) and 23 (IC50 = 5.59 ± 0.25 µM) were identified as the most potent inhibitors from the series. Compound 23 inhibited 17ß-HSD10 activity regardless of the substrate. It was found not cytotoxic toward the HEK-293 cell line and able to inhibit 17ß-HSD10 activity also in the cellular environment. Together, these findings support steroidal compounds as promising candidates for further development as 17ß-HSD10 inhibitors.
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1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
ACS Omega
Year:
2024
Document type:
Article
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