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

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Mar 18

PMID 38496976

Authors

Michaela Hanzlova

Barbora Slavikova

Marina Morozovova

Kamil Musilek

Aneta Rotterova

Lucie Zemanova

Eva Kudova

Affiliations

Soon will be listed here.

Abstract

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 (IC = 6.95 ± 0.35 μM) and (IC = 5.59 ± 0.25 μM) were identified as the most potent inhibitors from the series. Compound 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.

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