Synthesis, anticancer activity and mechanism of iron chelator derived from 2,6-diacetylpyridine bis(acylhydrazones).

We synthesized five iron chelator derived from 2,6-diacetylpyridine bis(acylhydrazones) and proved their iron complexes structure by X-ray single crystal diffraction. These ligands have a significant anticancer proliferative activity and low cytotoxicity against normal cells. The Fe(III) complexes show reduced cytotoxic activity compared to the metal-free ligands. Anticancer mechanism studies indicate that ligands with a potential anticancer proliferation activity by inhibiting the activity of ribonucleotide reductase. Ligand rather than iron complexes regulate the expression of cell cycle associated proteins and inhibit cell cycle arrest in S phase. Apoptosis mechanism results showed that both ligand and iron complexes did not significantly promote apoptosis.