Synthesis and Biological Evaluation of New Isoxazolyl Steroids as Anti-Prostate Cancer Agents
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73616108" target="_blank" >RIV/61989592:15310/22:73616108 - isvavai.cz</a>
Result on the web
<a href="https://www.mdpi.com/1422-0067/23/21/13534" target="_blank" >https://www.mdpi.com/1422-0067/23/21/13534</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms232113534" target="_blank" >10.3390/ijms232113534</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis and Biological Evaluation of New Isoxazolyl Steroids as Anti-Prostate Cancer Agents
Original language description
Steroids with a nitrogen-containing heterocycle in the side chain are known as effective inhibitors of androgen signaling and/or testosterone biosynthesis, thus showing beneficial effects for the treatment of prostate cancer. In this work, a series of 3 beta-hydroxy-5-ene steroids, containing an isoxazole fragment in their side chain, was synthesized. The key steps included the preparation of Weinreb amide, its conversion to acetylenic ketones, and the 1,2- or 1,4-addition of hydroxylamine, depending on the solvent used. The biological activity of the obtained compounds was studied in a number of tests, including their effects on 17 alpha-hydroxylase and 17,20-lyase activity of human CYP17A1 and the ability of selected compounds to affect the downstream androgen receptor signaling. Three derivatives diminished the transcriptional activity of androgen receptor and displayed reasonable antiproliferative activity. The candidate compound, 24j (17R)-17-((3-(2-hydroxypropan-2-yl)isoxazol-5-yl)methyl)-androst-5-en-3 beta-ol, suppressed the androgen receptor signaling and decreased its protein level in two prostate cancer cell lines, LNCaP and LAPC-4. Interaction of compounds with CYP17A1 and the androgen receptor was confirmed and described by molecular docking.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LX22NPO5102" target="_blank" >LX22NPO5102: National institute for cancer research</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
1422-0067
e-ISSN
1422-0067
Volume of the periodical
23
Issue of the periodical within the volume
21
Country of publishing house
CH - SWITZERLAND
Number of pages
32
Pages from-to
"13534-1"-"13534-32"
UT code for WoS article
000884037800001
EID of the result in the Scopus database
2-s2.0-85141883552