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

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).

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 = H, X = O) proved to be as efficient and less toxic as deferoxamine (DFO) when tested for its cytoprotective activity against iron overload.Figure optionsDownload as PowerPoint slide