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

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00584443" target="_blank" >RIV/61388963:_____/24:00584443 - isvavai.cz</a>

  • Alternative codes found

    RIV/62690094:18470/24:50021419

  • Result on the web

    <a href="https://doi.org/10.1021/acsomega.3c10148" target="_blank" >https://doi.org/10.1021/acsomega.3c10148</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1021/acsomega.3c10148" target="_blank" >10.1021/acsomega.3c10148</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

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

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10401 - Organic chemistry

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    ACS Omega

  • ISSN

    2470-1343

  • e-ISSN

    2470-1343

  • Volume of the periodical

    9

  • Issue of the periodical within the volume

    10

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    9

  • Pages from-to

    12116-12124

  • UT code for WoS article

    001177962600001

  • EID of the result in the Scopus database

    2-s2.0-85186408025