Thiosemicarbazones: The New Wave in Cancer Treatment

The anticancer effects of thiosemicarbazones were once solely attributed to the inhibition of ribonucleotide reductase, an enzyme involved in the rate-limiting step of DNA synthesis. However, the mechanism behind this inhibition was initially not described. The ability of thiosemicarbazones to chelate metal ions has now been recognized as a major factor in their antiproliferative effects. This mini-review discusses current advances of an emerging 'new wave' of thiosemicarbazones as potent anticancer agents, describing recent insights into their mechanism of action. The redox activity of Fe-thiosemicarbazone complexes is critical in their anticancer activity, resulting in oxidative damage and the inhibition of ribonucleotide reductase. In vivo analysis indicates that some thiosemicarbazones show potential as chemotherapeutic agents.