Exploring alternative Zn-binding groups in the design of HDAC inhibitors: Squaric acid, N-hydroxyurea, and oxazoline analogues of SAHA

Analogues of suberoylanilide hydroxamic acid (SAHA) were prepared by replacing the Zn-binding group with squaric acid, N-hydroxyurea, and 4-hydroxymethyl oxazoline units, also varying the length of the aliphatic chain. No inhibitory activity on HDAC was observed below 1.0 μM and no cytotoxic activity on different tumor cell lines was seen below 20.0 μM.

Analogues of suberoyl anilide hydroxamic acid (SAHA) were prepared by replacing the Zn-binding group with squaric acid, N-hydroxyurea, and 4-hydroxymethyl oxazoline, also varying the length of the aliphatic chain.Figure optionsDownload as PowerPoint slide