Isoform-selective HDAC1/16/8 inhibitors with an imidazo-ketopiperazine cap containing stereochemical diversity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F18%3A00106141" target="_blank" >RIV/00216224:14310/18:00106141 - isvavai.cz</a>

Výsledek na webu

<a href="https://royalsocietypublishing.org/doi/10.1098/rstb.2017.0364" target="_blank" >https://royalsocietypublishing.org/doi/10.1098/rstb.2017.0364</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1098/rstb.2017.0364" target="_blank" >10.1098/rstb.2017.0364</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Isoform-selective HDAC1/16/8 inhibitors with an imidazo-ketopiperazine cap containing stereochemical diversity

Popis výsledku v původním jazyce

A series of hvdroxamic acids linked by different lengths to a chiral imidazo-ketopiperazine scaffold were synthesized. The compounds with linker lengths of 6 and 7 ca vb on atoms were the most potent in histone deacetylase (HDAC) inhibition, and were specific submicromolar inhibitors of the HDAC1, HDAC6 and HDAC8 isoforms. A docking model for the binding mode predicts binding of the hvdroxamic acid to the active site zinc cation and additional interactions between the imidazo-ketopiperazine and the enzyme rim. The compounds were micromolar inhibitors of the MV4-11, THP-1 and U937 cancer cell lines. Increased levels of histone H3 and tubulin acetylation support a cellular mechanism of action through HDAC inhibition. This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.

Název v anglickém jazyce

Isoform-selective HDAC1/16/8 inhibitors with an imidazo-ketopiperazine cap containing stereochemical diversity

Popis výsledku anglicky

A series of hvdroxamic acids linked by different lengths to a chiral imidazo-ketopiperazine scaffold were synthesized. The compounds with linker lengths of 6 and 7 ca vb on atoms were the most potent in histone deacetylase (HDAC) inhibition, and were specific submicromolar inhibitors of the HDAC1, HDAC6 and HDAC8 isoforms. A docking model for the binding mode predicts binding of the hvdroxamic acid to the active site zinc cation and additional interactions between the imidazo-ketopiperazine and the enzyme rim. The compounds were micromolar inhibitors of the MV4-11, THP-1 and U937 cancer cell lines. Increased levels of histone H3 and tubulin acetylation support a cellular mechanism of action through HDAC inhibition. This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10602 - Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES

ISSN

0962-8436

e-ISSN

—

Svazek periodika

373

Číslo periodika v rámci svazku

1748

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

7

Strana od-do

1-7

Kód UT WoS článku

000430738400018

EID výsledku v databázi Scopus

2-s2.0-85045928462