Perrino Elena, Cappelletti Graziella, Tazzari Valerio, Giavini Erminio, Del Soldato Piero, Sparatore Anna
Sulfidris s.r.l., Viale Gran Sasso 17, 20131 Milan, Italy.
Bioorg Med Chem Lett. 2008 Mar 15;18(6):1893-7. doi: 10.1016/j.bmcl.2008.02.007. Epub 2008 Feb 8.
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.
合成了一种二硫代硫酮和两种丙戊酸（VPA）的新型甲硫基磺酸盐衍生物，并在体外作为组蛋白脱乙酰酶（HDAC）抑制剂进行了测试。这些新分子及其硫化部分对HDAC酶活性、抗增殖活性和组蛋白高乙酰化的抑制作用比VPA强得多。ACS 2是新型VPA衍生物中最有趣的化合物，其硫化部分5-（4-羟基苯基）-3H-1,2-二硫代-3-硫酮（也已知是茴芹内酯三硫酮的一种代谢物）似乎对其活性有显著贡献。这是首次报道二硫代硫酮和硫代磺酸盐具有HDAC抑制活性。
