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).
Rodriguez-Lucena
David
D
Métaux et Microorganismes: Chimie, Biologie et Applications, IREBS FRE3211-CNRS/Université de Strasbourg, ESBS, Boulevard Sébastien Brant, F-67400 Illkirch, France.
Gaboriau
François
F
Rivault
Freddy
F
Schalk
Isabelle J
IJ
Lescoat
Gérard
G
Mislin
Gaëtan L A
GL
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007502:Iron Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007502:Iron Chelating Agents; D013438:Sulfhydryl Compounds; D013844:Thiazoles; C548618:bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamide; D003676:Deferoxamine