New sulfurated derivatives of valproic acid with enhanced histone deacetylase inhibitory activity.
Bioorg Med Chem Lett
; 18(6): 1893-7, 2008 Mar 15.
Article
in En
| MEDLINE
| ID: mdl-18294844
ABSTRACT
One dithiolthione and two new methanethiosulfonate derivatives of valproic acid (VPA) were synthesized and tested in vitro as histone deacetylase (HDAC) inhibitors. The new molecules, as well as their sulfurated moieties, exhibited a much stronger inhibition of HDAC enzymatic and antiproliferative activities and histone hyperacetylation than VPA. ACS 2 is the most interesting compound among the new VPA derivatives and its sulfurated moiety, 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione, also known to be a metabolite of anethole trithione, seems to contribute significantly to its activity. This is the first time that HDAC inhibitory activity is described for dithiolethiones and thiosulfonates.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Valproic Acid
/
Enzyme Inhibitors
/
Histone Deacetylase Inhibitors
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2008
Type:
Article
Affiliation country:
Italy