title: New sulfurated derivatives of valproic acid with enhanced histone deacetylase inhibitory activity.
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.
authors.affiliation: Sulfidris s.r.l., Viale Gran Sasso 17, 20131 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Perrino
authors.forename: Graziella
authors.initials: G
authors.lastname: Cappelletti
authors.forename: Valerio
authors.initials: V
authors.lastname: Tazzari
authors.forename: Erminio
authors.initials: E
authors.lastname: Giavini
authors.forename: Piero
authors.initials: P
authors.lastname: Del Soldato
authors.forename: Anna
authors.initials: A
authors.lastname: Sparatore
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013886:Thiosulfonic Acids / Q000737:chemistry; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014635:Valproic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C529309:ACS2 compound; C529310:ACS33 compound; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D013886:Thiosulfonic Acids; D014635:Valproic Acid