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

Md Shahidul Islam; Md Nurul Islam; Md Ashraful Hoque; Norikazu Nishino; Tamaki Kato; Hyun-Jung Kim; Akihiro Ito; Minoru Yoshida

doi:10.1016/j.bioorg.2015.02.009

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

Bioorg Chem. 2015 Apr:59:145-50. doi: 10.1016/j.bioorg.2015.02.009. Epub 2015 Mar 7.

Authors

Md Shahidul Islam¹, Md Nurul Islam², Md Ashraful Hoque³, Norikazu Nishino⁴, Tamaki Kato⁴, Hyun-Jung Kim⁵, Akihiro Ito⁶, Minoru Yoshida⁶

Affiliations

¹ Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan; Department of Chemistry, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh. Electronic address: shahidulchem@yahoo.com.
² Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan; Department of Chemistry, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh.
³ Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh.
⁴ Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.
⁵ BioRunxInc., Seoul 110-749, Republic of Korea.
⁶ Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Saitama 351-0198, Japan.

PMID: 25797804
DOI: 10.1016/j.bioorg.2015.02.009

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; SK-658 analogs; SS-hybrid; Zinc binding group.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Histone Deacetylase Inhibitors / chemical synthesis
Histone Deacetylase Inhibitors / chemistry*
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / chemistry
Histone Deacetylases / metabolism
Humans
Hydroxamic Acids / chemistry*
Hydroxamic Acids / pharmacology*
Models, Molecular
Structure-Activity Relationship
Zinc / metabolism

Substances

Histone Deacetylase Inhibitors
Hydroxamic Acids
Histone Deacetylases
Zinc