title: Modular synthesis and biological activity of pyridyl-based analogs of the potent Class I Histone Deacetylase Inhibitor Largazole.
abstract: The formation of a series of analogs containing a pyridine moiety in place of the natural thiazole heterocycle, based on the potent, naturally occurring HDAC inhibitor Largazole has been accomplished. The synthetic strategy was designed modularly to access multiple inhibitors with different aryl functionalities containing both the natural depsipeptide and peptide isostere variant of the macrocycle. The cytotoxicity and biochemical activity of the library of HDAC inhibitors is described herein.
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Dane J
authors.initials: DJ
authors.lastname: Clausen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Smith
authors.affiliation: Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Brandon E
authors.initials: BE
authors.lastname: Haines
authors.affiliation: Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Olaf
authors.initials: O
authors.lastname: Wiest
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; University of Colorado Cancer Center, Aurora, CO 80045, USA. Electronic address: robert.williams@colostate.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Williams
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; D013844:Thiazoles; C527895:largazole; D006655:Histone Deacetylases; C023666:pyridine
keywords: Class I Histone Deacetylase Inhibitor; Cytotoxic and biochemical assays; Largazole; Pyridine analogs