An efficient synthesis of SK-658 and its analogs as potent histone deacetylase inhibitors

• SK-658 analogs having thioester and SS-hybrid groups were synthesized.
• All the compounds were active in nano molar range.
• Disulfide compounds displayed impressive HDAC inhibitory activity.
• Easy synthesis and excellent activity make them to be potential drug candidates.

SK-658 is a potent histone deacetylase (HDAC) inhibitor that showed higher activity than SAHA due to the presence of extended hydrophobic group. We designed and synthesized thioester and SS-hybrid bearing SK-658 analogs as HDAC inhibitors. All the compounds were active in nano molar range and showed higher inhibitory activity than SAHA and SK-658. Among these, disulfide compounds showed the highest activity.

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