Synthesis and biological properties of iron chelators based on a bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamide or -thiocarboxamide (BHPTC) scaffold.

David Rodriguez-Lucena (1) , François Gaboriau (2) , Freddy Rivault (1) , Isabelle J Schalk (1) , Gérard Lescoat (2) , Gaëtan L A Mislin (1)

1 Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique
2 Foie, métabolismes et cancer

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).

Mots clés: Iron chelator; Cancer; Iron chelation therapy; Thioamide

Domaines: Hépatologie et Gastroentérologie

David Rodriguez-Lucena, François Gaboriau, Freddy Rivault, Isabelle J Schalk, Gérard Lescoat, et al.. Synthesis and biological properties of iron chelators based on a bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamide or -thiocarboxamide (BHPTC) scaffold.. Bioorganic and Medicinal Chemistry, 2010, 18 (2), pp.689-95. ⟨10.1016/j.bmc.2009.11.057⟩. ⟨hal-00742476⟩