1 research outputs found
C‑3 Steroidal Hemiesters as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 10
17β-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 17β-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 17β-HSD10 converting 17β-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 17β-HSD10 activity regardless of the substrate.
It was found not cytotoxic toward the HEK-293 cell line and able to
inhibit 17β-HSD10 activity also in the cellular environment.
Together, these findings support steroidal compounds as promising
candidates for further development as 17β-HSD10 inhibitors