Hydroxamates of para-aminobenzoic acid as selective inhibitors of HDAC8

• Twelve compounds (4a–4l) were tested for their HDAC inhibitory activity.
• All twelve compounds selectively inhibited the HDAC8.
• 4b, 4e & 4l resembled the piperazine derivatives reported earlier.
• 4f & 4k were found to inhibit HDAC8 at a concentration below 20 μM.

A series of hydroxamates (4a–4l) were prepared from p-aminobenzoic acid to inhibit HDAC8. The idea is to substitute rigid aromatic ring in place of less rigid piperazine ring of hydroxamates reported earlier by our group. It is expected to increase potency retaining the selectivity. Result obtained suggested that the modifications carried out retained the selectivity towards HDAC8 isoform and increasing the potency in very few cases. Increase in potency is also associated with variation in cap aryl region. Two compounds (4f & 4l) were found to inhibit HDAC8 at concentrations (IC50) less than 20 μM.

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