Largazole and Analogues with Modified Metal-Binding Motifs Targeting Histone Deacetylases: Synthesis and Biological Evaluation

Inhibitors of Histone Deacetylases represent promising anti-cancer agents. HDAC proteins are a familly of 18 enzymes and they exhibit a high homology within their catalytic sites, rendering specific targeting of one protein really challenging. They developed an efficient route to largazole analogues. They investigated the properties of chelation with Zinc cation.
The compounds they made were less active than largazole, however they show some selectivity toward the class I of HDACs.