title: Suberoylanilide hydroxamic acid, a potent histone deacetylase inhibitor; its X-ray crystal structure and solid state and solution studies of its Zn(II), Ni(II), Cu(II) and Fe(III) complexes.
abstract: Reaction of the potent hydroxamate-based histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), with hydrated metal salts of Fe(III), Cu(II), Ni(II) and Zn(II) yielded a tris-hydroxamato complex in the case of Fe(III) and bis-hydroxamato complexes in the case of Cu(II), Ni(II) and Zn(II) both in the solid state and in solution. Reaction of the secondary hydroxamic acid, N-Me-SAHA, also yielded a tris-hydroxamato complex in the case of Fe(III) and bis-hydroxamato complexes in the case of Cu(II), Ni(II) and Zn(II) in solution. These metal complexes have the hydroxamato moiety coordinated in an O,O'-bidentate fashion. Stability constants of the metal complexes formed with SAHA and N-Me-SAHA in a DMSO/H(2)O 70/30%(v/v) mixture are described. A novel crystal structure of SAHA together with a novel synthesis for N-Me-SAHA are also reported.
authors.affiliation: Centre for Synthesis & Chemical Biology, Department of Pharmaceutical & Medicinal Chemistry, Royal College of Surgeons in Ireland, Dublin, Ireland. dgriffith@rcsi.ie
authors.forename: Darren M
authors.initials: DM
authors.lastname: Griffith
authors.forename: Béla
authors.initials: B
authors.lastname: Szocs
authors.forename: Tomás
authors.initials: T
authors.lastname: Keogh
authors.forename: Kyrill Yu
authors.initials: KY
authors.lastname: Suponitsky
authors.forename: Etelka
authors.initials: E
authors.lastname: Farkas
authors.forename: Péter
authors.initials: P
authors.lastname: Buglyó
authors.forename: Celine J
authors.initials: CJ
authors.lastname: Marmion
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D005290:Ferric Compounds / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006877:Hydroxamic Acids / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D000077337:Vorinostat; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D009942:Organometallic Compounds; D000077337:Vorinostat; D003300:Copper; D009532:Nickel; D015032:Zinc