Synthesis and estrogenic activity of BODIPY-labeled estradiol conjugates
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F24%3A73625161" target="_blank" >RIV/61989592:15310/24:73625161 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0928098724001258" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0928098724001258</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejps.2024.106813" target="_blank" >10.1016/j.ejps.2024.106813</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis and estrogenic activity of BODIPY-labeled estradiol conjugates
Original language description
Novel BODIPY–estradiol conjugates have been synthesized by selecting position C-3-O for labeling. The conjugation strategy was based on Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) or etherification. Estradiol derivatives used as azide partners bearing an ω-azidoalkyl function through C4–C8-long linkers have been prepared. CuAAC reactions of estradiol azides with BODIPY alkyne furnished fluorescent 3-O-labeled conjugates bearing the triazole ring as a coupling moiety. Williamson etherifications of 3-O-(ω-bromoalkyl)-17β-estradiol derivatives with BODIPY-OH resulted in labeled conjugates connected with an ether moiety. Interactions of the conjugates with estrogen receptor (ER) were investigated using molecular docking calculations in comparison with estradiol.The conjugates occupied both the classical and alternative binding sites on human ERα, with slightly lower binding affinity to references estradiol and diethystilbestrol. All compounds have displayed reasonable estrogenic activity. They increased the proliferation of ER-positive breast cancer cell line MCF7 contrary to ER-negative SKBR-3 cell line. The most potent compound 13a induced the transcriptional activity of ER in dose-dependent manner in dual luciferase recombinant reporter model and increased progesterone re-ceptor’s expression, proving the retained estrogenic activity. The fluorescence of candidate compound 13a colocalised with the ERα. The newly synthesized labeled compounds might serve as good starting point for further development of fluorescent probes for modern biological applications. In addition to studying steroid uptake and transport in cells, e.g. in the processes of biodegradation of estrogen-hormones micropollutants, they could also be utilized in examination of estrogen-binding proteins.
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
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach
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
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
ISSN
0928-0987
e-ISSN
1879-0720
Volume of the periodical
199
Issue of the periodical within the volume
AUG
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
12
Pages from-to
"106813-1"-"106813-12"
UT code for WoS article
001249651100001
EID of the result in the Scopus database
2-s2.0-85194971433