Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 105, Issue 6, Pages 763-769Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2011.03.003
Keywords
Metalloenzyme; Histone deacetylase inhibitor; Anti-cancer agent; Metal complexes; Hydroxamic acids
Funding
- Science Foundation Ireland [07/RFP/CHEF570, 08/RFP/CHE1675]
- Hungarian Scientific Research Funds [OTKA K76142, TAMOP 4.2.1./B-09/1/KONV-2010-0007]
- Programme for Research in Third Level Institutions (PRTLI)
- Science Foundation Ireland (SFI) [07/RFP/CHEF570, 08/RFP/CHE1675] Funding Source: Science Foundation Ireland (SFI)
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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. (C) 2011 Elsevier Inc. All rights reserved.
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