当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and biological evaluation of novel hydroxamic acid based histone deacetylase 6 selective inhibitors bearing phenylpyrazol scaffold as surface recognition motif.

Design, synthesis and biological evaluation of novel hydroxamic acid based histone deacetylase 6 selective inhibitors bearing phenylpyrazol scaffold as surface recognition motif.

Abstract：

:In recent years, inhibition of HDAC6 became a promising therapeutic strategy for the treatment of cancer and HDAC6 inhibitors were considered to be potent anti-cancer agents. In this work, celecoxib showed moderate degree of HDAC6 inhibition activity and selectivity in preliminary enzyme inhibition activity assay. A series of hydroxamic acid derivatives bearing phenylpyrazol moiety were designed and synthesized as HDAC6 inhibitors. Most compounds showed potent HDAC6 inhibition activity. 11i was the most selective compound against HDAC6 with IC50 values of 0.020µM and selective factor of 101.1. Structure-activity relationship analysis indicated that locating the linker group at 1' of pyrazol gave the most selectivity. The most compounds 11i (GI50=3.63μM) exhibited 6-fold more potent than vorinostat in HepG2 cells. Considering of the high selectivity against HDAC6 and anti-proliferation activity, such compounds have potential to be developed as anti-cancer agents.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Yang J,Cheng G,Xu Q,Luan S,Wang S,Liu D,Zhao L

doi

10.1016/j.bmc.2017.08.029

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

1418-1425

issue

8

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)31490-6

journal_volume

26

pub_type

杂志文章

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