Novel selective indole based histone deacetylase 10 inhibitors as anticancer therapeutics

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel selective indole based histone deacetylase 10 inhibitors as anticancer therapeutics

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Novel selective indole based histone deacetylase 10 inhibitors as anticancer therapeutics

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

2045-2322

Svazek periodika

15

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

17

Strana od-do

33307

Kód UT WoS článku

001582550500031

EID výsledku v databázi Scopus

2-s2.0-105017417357