Iron-chelating Anticancer Drugs
ironjustice
based on a bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamide
or -thiocarboxamide (BHPTC) scaffold
David Rodriguez-Lucenaa, François Gaboriaub, Freddy Rivaulta,
Isabelle J. Schalka, Gérard Lescoatb and Gaëtan L.A. Mislina, ,
aMétaux et Microorganismes : Chimie, Biologie et Applications,
IREBS FRE3211-CNRS/Université de Strasbourg, ESBS,
Boulevard Sébastien Brant, F-67400 Illkirch, France.
bFer et Foie : Aspects Physiologiques et Pathologiques U 991 –
INSERM/EA « MDC »/Université de Rennes 1, Hôpital Pontchaillou - 2,
rue Henri Le Guilloux, F-35033 Rennes Cedex, France.
Received 20 July 2009; revised 17 November 2009;
accepted 28 November 2009.
Available online 6 December 2009.
Abstract
Bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamides and
-thiocarboxamides (BHPTCs) form a family of gemini
hexacoordinated bis-tridentate chelating scaffolds.
Four molecules were synthesized and shown to chelate
iron(III) efficiently with a 1:1 stoichiometry.
A dithioamide BHPTC displayed promising antiproliferative
activity in several cancerous cell lines, making this
molecule an interesting lead compound for the design of
new iron-chelating anticancer drugs.
Conversely, diamide BHPTCs had significant cytoprotective
activity against iron overload in HepaRG cells in vitro, and
were as efficient as and less toxic than deferoxamine B
(DFO).
Graphical abstract
Bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamides or
–thiocarboxamides (BHPTCs) are efficient bis-tridentate
iron chelators with promising biological properties :
lipophilic dithioamide BHPTC (R= CH3, X = S) displayed
in vitro an antiproliferative activity on several cancerous
cell lines when hydrophilic diamide BHPTC (R=OH, X=O)
proved to be as efficient and less toxic as deferoxamine
(DFO) when tested for its cytoprotective activity against
iron overload.
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