Thiosemicarbazones: the new wave in cancer treatment

Abstract

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.