title: Phosphorus-based SAHA analogues as histone deacetylase inhibitors.
abstract: [structure: see text] Three analogues of suberoyl anilide hydroxamic acid (SAHA) with phosphorus metal-chelating functionalities were synthesized as inhibitors of histone deacetylases (HDACs). The compounds showed weak activity for HeLa nuclear extracts (IC(50) = 0.57-6.1 mM), HDAC8 (IC(50) = 0.28-0.41 mM), and histone-deacetylase-like protein (HDLP, IC(50) = 0.33-1.9 mM), suggesting that the transition state of HDAC is not analogous to zinc proteases. Antiproliferative activity against A2780 cancer cells (IC(50) = 0.11-0.12 mM), comparable to SAHA (0.15 mM), was observed.
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061-0212, USA.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Kapustin
authors.forename: György
authors.initials: G
authors.lastname: Fejér
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gronlund
authors.forename: Dewey G
authors.initials: DG
authors.lastname: McCafferty
authors.forename: Edward
authors.initials: E
authors.lastname: Seto
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Etzkorn
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D002467:Cell Nucleus / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D000077337:Vorinostat