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

Bioorg Med Chem. 2010 Jan 15;18(2):689-95. doi: 10.1016/j.bmc.2009.11.057. Epub 2009 Dec 6.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Deferoxamine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Screening Assays, Antitumor
  • Humans
  • Iron Chelating Agents / chemical synthesis*
  • Iron Chelating Agents / chemistry
  • Iron Chelating Agents / pharmacology*
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemistry*
  • Thiazoles / chemistry*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Iron Chelating Agents
  • Sulfhydryl Compounds
  • Thiazoles
  • bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamide
  • Deferoxamine