Related Experiment Video
Updated: Jul 10, 2026

Quantifiable and Inexpensive Cell-Free Fluorescent Method to Confirm the Ability of Novel Compounds to Chelate Iron
Published on: February 23, 2024
Design, synthesis, and characterization of new iron chelators with anti-proliferative activity: structure-activity
Danuta S Kalinowski1, Philip C Sharpe, Paul V Bernhardt
1Iron Metabolism and Chelation Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
Abstract:
Di-2-pyridylketone isonicotinoyl hydrazone Fe chelators utilize the N,N,O-donor set and have moderate anti-proliferative effects. Their closely related N,N,S-thiosemicarbazone analogues, namely, the di-2-pyridylketone thiosemicarbazones, exhibit markedly increased anti-proliferative and redox activity, and this was thought to be due to the inclusion of a sulfur donor atom (Richardson, D. R. et al. J. Med. Chem. 2006, 49, 6510-6521). To further examine the effect of donor atom identity on anti-proliferative activity, we synthesized thiohydrazone analogues of extensively examined aroylhydrazone chelators. The O,N,S-thiohydrazones exhibited decreased anti-proliferative effects compared to their parent aroylhydrazones and reduced redox activity. In contrast, the N,N,S-thiohydrazones showed vastly increased anti-proliferative activity compared to their hydrazone analogues, being comparable to potent thiosemicarbazones. Additionally, N,N,S-thiohydrazone complexes had reversible FeIII/II couples and exhibited increased redox activity. These observations demonstrate that the N,N,S-donor set is critical for potent anti-proliferative efficacy.
Related Concept Videos
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Antiprotozoal Agents
Metal-Ligand Bonds
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
Inhibitors of Bacterial DNA Synthesis
EDTA: Chemistry and Properties
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...

