Aminoguanidine Based Iron Chelators for Cancer Therapy

Abraham Domb, Medicinal Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
Arijit Basu, Medicinal Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

Thiosemicarbazones and semicarbazone derivatives have shown strong complexation to iron, cupper, and other metal ions essential for the propagation of tumor cells. Several thiosemicarbazone derivatives have shown strong anticancer activity and are under preclinical development. While the oxy and thio derivatives of semicarbazone have been extensively investigated, little was reported on the guanidino derivatives as iron chelators and treatment of cancer.

The corresponding aminoguanidine derivatives of the most effective thiosemicarbazones have been synthesized and tested for antitumor activity and for iron and cupper complexation. The corresponding aminoguanidine derivatives of the most effective thiosemicarbazone are given in Scheme 1.

Scheme 1: Thiosemicarbazone and its proposed aminoguanidine derivatives
The aminoguanidine derivatives were synthesized from either aminoguanidine or from thiosemicarbazide. Several derivatives showed strong chelation to iron and copper ions as well as anticancer activity in vitro.