Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes

Maram T Basha; Jeane Bordini; Des R Richardson; Manuel Martinez; Paul V Bernhardt

doi:10.1016/j.jinorgbio.2015.12.004

Back

Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes

Journal article

Peer reviewed

Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes

Maram T Basha, Jeane Bordini, Des R Richardson, Manuel Martinez and Paul V Bernhardt

Journal of inorganic biochemistry, Vol.162, pp.326-333

01/09/2016

DOI: https://doi.org/10.1016/j.jinorgbio.2015.12.004

PMID: 27079328

Abstract

Antineoplastic Agents - chemistry

Coordination Complexes - chemistry

Humans

Iron - chemistry

Iron Chelating Agents - chemistry

Kinetics

Methemoglobin - chemistry

Models, Molecular

Oxidation-Reduction

Oxyhemoglobins - chemistry

Protein Structure, Secondary

Pyridines - chemistry

Solutions

Structure-Activity Relationship

Thiosemicarbazones - chemistry

The oxidation of human oxyhemoglobin (HbO ) to methemoglobin (metHb) is an undesirable side effect identified in some promising thiosemicarbazone anti-cancer drugs. This is attributable to oxidation reactions driven by Fe complexes of these drugs formed in vivo. In this work the Fe complexes of selected 2-benzoylpyridine thiosemicarbazones (HBpT), 2-acetylpyridine thiosemicarbazones (HApT), and the clinically trialled thiosemicarbazone, Triapine® (3-amino-2-pyridinecarboxaldehyde thiosemicarbazone, H3-AP), have been studied. This was achieved by time-resolved UV-Visible absorption spectroscopy and the sequential oxidation of the α- and β-chains of HbO at distinctly different rates has been identified. A key structural element, namely a terminal -NH group on the thiosemicarbazone moiety, was found to be an important common feature of the most active HbO oxidising complexes that were investigated. Therefore, these studies indicate that an unsubstituted -NH moiety at the terminus of the thiosemicarbazone group should be avoided in the design of future compounds from this class.

Metrics

1 Record Views

Details

Title: Kinetico-mechanistic studies on methemoglobin generation by biologically active thiosemicarbazone iron(III) complexes
Creators - without role: Maram T Basha - University of Queensland
Jeane Bordini - University of Queensland
Des R Richardson - University of Sydney
Manuel Martinez - Universitat de Barcelona
Paul V Bernhardt - University of Queensland
Publication Details: Journal of inorganic biochemistry, Vol.162, pp.326-333
Identifiers: 9932912208331
Academic Unit: University of Jeddah
Language: English
Resource Type: Journal article