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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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'.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

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

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

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

Name of the periodical

PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES

ISSN

0962-8436

e-ISSN

—

Volume of the periodical

373

Issue of the periodical within the volume

1748

Country of publishing house

GB - UNITED KINGDOM

Number of pages

7

Pages from-to

1-7

UT code for WoS article

000430738400018

EID of the result in the Scopus database

2-s2.0-85045928462