Exploration of 4-(1H-indol-3-yl)cyclohex-3-en-1-amine analogues as HDAC inhibitors: Design, synthesis, biological evaluation and modelling studies.
Bioorg Med Chem Lett
; 72: 128846, 2022 09 15.
Article
in En
| MEDLINE
| ID: mdl-35697181
Epigenetics regulate the gene expression and chromatin organization associated with the development and occurrence of cancer. Histone deacetylase inhibitors (HDACis) have been proved to be an effective epigenetic targeting drug for cancer treatment. The structures of most HDACis were divided into four parts, including cap group, connection unit, linker region and zinc binding group. We designed a series of compounds containing the structure of phenoxyacetate for the linker region and cyclohexene for connection unit as a novel type of inhibitors. Representative compound YZ1 exhibited obvious antiproliferative activity against four different cell lines and potent enzymatic inhibitory activities to class I HDACs, which IC50 of HDAC1-3 were 1.6 nM, 1.9 nM and 3.8 nM respectively. In addition, YZ1 concentration-dependently inhibited cell proliferation, induced apoptosis and cycle arrest at G2/M phase in HCT116 cells. With biological activity assessment and docking studies, these results indicate YZ1 has the potential to be a lead compound for further optimization as HDAC inhibitors.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histone Deacetylase Inhibitors
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2022
Document type:
Article
Country of publication:
United kingdom