Iron, due to its unique biochemical and biophysical properties is present in the most important processes within human cells. The transportation of oxygen and its presence in complex proteins, such as transferrin and ferritin, can be used to highlight the role of iron. It is proven that most of cancer cells have a higher requirement for iron than normal cells as they rapidly proliferate. Hence, iron metabolism is altered within these cells. This fact is reflected by higher number of Tf receptors on their cell surface, mediating a high rate of iron uptake.

All compounds were synthesized in microwave reactor (CEM-DISCOVERY^®) and the purity of final products was determinated by HPLC. The stereochemistry and structures of final compounds were confirmed by NMR spectroscopy and HRMS spectroscopy.

To sum up, novel iron chelators based on thiosemicarbazone moiety have been synthesized and tested for antiproliferative activity. Theywere found to be active against HCT116 p53+/+and p53 -/- and SK-N-MC cancer cells (nanomolar cytotoxicity).Moreover the ability to induce cellular iron release and inhibit iron uptake from the iron-binding protein, transferrin, was at the same level that most active iron chelator Dp44mT [1,2]

References:                                  

[1]. M.Serda, Polish Patent Application, 2010, P391681.

[2]. M.Serda, Polish Patent Application, 2011, P.396353

Acknowledgments:

Maciej Serda was supported by a TWING fellowship and NCN grant DEC-2011/01/N/NZ4/01166. Anna Mrozek-Wilczkiewicz appreciates the support of UPGOW fellowship and NCN grant N405/068440.

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