title: Bicyclic tetrapeptide histone deacetylase inhibitors with methoxymethyl ketone and boronic acid zinc-binding groups.
abstract: Histone deacetylase (HDAC) inhibitors are a class of potential therapeutics for the treatment of cancer. Bicyclic tetrapeptides equipped with methoxymethyl ketone and boronic acid as zinc-binding group were designed and synthesized. The inhibitory activities of these compounds were evaluated against HDAC enzymes. The cell-free and cell-based assay data showed that both potency and selectivity changed with the change in zinc-binding group. Boronic acid-based compound showed poor activity whereas methoxymethyl ketone-based compound displayed impressive activity in both cell-free and cell-based conditions.
authors.affiliation: 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: mnurulchem@gmail.com.
authors.forename: Md Nurul
authors.initials: MN
authors.lastname: Islam
authors.affiliation: 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.
authors.forename: Md Shahidul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: 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.
authors.forename: Md Ashraful
authors.initials: MA
authors.lastname: Hoque
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Kato
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Nishino
authors.affiliation: Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Saitama 351-0198, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.affiliation: Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Saitama 351-0198, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D001665:Binding Sites; D001897:Boronic Acids / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007659:Ketones / Q000378:metabolism; D008745:Methylation; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism
chemical_list: D001897:Boronic Acids; D056572:Histone Deacetylase Inhibitors; D007659:Ketones; D009842:Oligopeptides; D006655:Histone Deacetylases; D015032:Zinc
keywords: Bicyclic tetrapeptides; Boronic acid; Histone deacetylase inhibitors; Methoxymethyl ketone; Ring-closing metathesis