Design and synthesis of thiazole-5-hydroxamic acids as novel histone deacetylase inhibitors

We have designed and synthesized a series of structurally novel hydroxamic acid-based histone deacetylase (HDAC) inhibitors characterized by a zinc chelating head group attached directly to a thiazole ring. The thiazole ring connects to a piperazine spacer, which is capped with a sulfonamide group. These novel molecules potently inhibit an HDAC enzyme mixture derived from HeLa cervical carcinoma cells and show potent antiproliferative activity against the breast cancer cell line MCF7.

The synthesis, histone deacetylase (HDAC) inhibitory activity and the antiproliferative activity of thiazole-5-hydroxamic acids 6–9 are described.Figure optionsDownload as PowerPoint slide