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An efficient synthesis of SK-658 and its analogs as potent histone deacetylase inhibitors
Institution:1. Department of Biochemistry & Molecular Biology, University of Georgia, Athens, GA 30602, USA;2. Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, GA 30602, USA;3. Department of Biochemistry, University of Kassel, Germany;4. Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada;5. Department of Chemistry & Biochemistry and Pharmacology, University of CA, San Diego, USA;6. INSERM U1016, CNRS UMR8104, Cochin Institute, Paris, 75014 France;7. Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes - Sorbonne Paris Cité, France;8. Institute of Bioinformatics, University of Georgia, Athens, GA 30602, USA
Abstract: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.
Keywords:Histone deacetylase inhibitor  Zinc binding group  SK-658 analogs  SS-hybrid
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