Novel selective indole based histone deacetylase 10 inhibitors as anticancer therapeutics
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F25%3A00640257" target="_blank" >RIV/86652036:_____/25:00640257 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41598-025-02774-6" target="_blank" >https://www.nature.com/articles/s41598-025-02774-6</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-025-02774-6" target="_blank" >10.1038/s41598-025-02774-6</a>
Alternative languages
Result language
angličtina
Original language name
Novel selective indole based histone deacetylase 10 inhibitors as anticancer therapeutics
Original language description
Histone deacetylase (HDAC) inhibitors represent a promising class of anti-cancer agents that play a key role in both epigenetic and non-epigenetic regulation, leading to cancer cell death, apoptosis, and cell cycle arrest. This study synthesized novel bicyclic hydroxamic acid derivatives and evaluated their inhibitory and selectivity activity against class I and IIb HDACs. Our findings demonstrate that Compound 2e specifically inhibits HDAC10 with high selectivity over HDAC6, while shows no significant impact on class I HDACs. Compound 2a exhibited the most potant inhibitory activity against HDAC10, with IC50 0.41 +/- 0.02 nM. In contrast, Compound 2f revealed a preference toward HDAC6, with an IC50 value of 2.5 +/- 0.3 nM. Compounds 2c and 2d demonstrated high selectivity toward class IIb over class I HDACs. Docking and molecular dynamics studies revealed that compound 2a fits well into the active site of HDAC10, forming stable and strong interactions with key residues F204, D94, W205, and E274 in HDAC10. In addition, we assessed the anti-proliferative activity these compounds against a panel of four human solid tumor cell lines. To evaluate their selectivity, non-cancerous kidney cell lines (LLC-PK1 and VERO) were employed to determine the effects of these compounds on normal cell proliferation.
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
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Scientific Reports
ISSN
2045-2322
e-ISSN
2045-2322
Volume of the periodical
15
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
17
Pages from-to
33307
UT code for WoS article
001582550500031
EID of the result in the Scopus database
2-s2.0-105017417357