Mechanism of Action of Anticancer Metallodrugs

Herein the anticancer mechanisms of action from platinum and essential metals compounds are discussed. In the second half of last century, the cytotoxic activity of the cisplatin [cis-dichloro, diamin platinum (II)] was discovered and the use as anticancer drugs of this compound was proposed. For several decades, the inorganic anticancer drug seemed excellent. Nevertheless, undesired side effects such as toxicity and resistance to the drug shadowed its success. To accomplish an increased anticancer activity and a lower toxicity, several analogues such as carboplatin and oxaliplatin were developed as antineoplastic drugs. Research in the platinum metal group was developed rapidly; palladium, ruthenium, osmium, and rhodium. However, an innovative approach was developed by the use of essential metals compounds as an alternative to reduce the toxicity and resistance induced by the platinum compounds. Iron and copper were the first essential metal compounds studied. The term “metals” in medicine was emerging at that moment and later on, the term Metallodrug was acquired. Some other essential metals have been studied and proposed as metallodrugs. Regarding the mechanism of action, at first, interaction with DNA was thoroughly studied and research leads to the proposal of adducts formation by direct bond between platinum and DNA bases mainly. Later on, cell death by means of apoptosis was mentioned, and therefore, the formation of reactive species of oxygen was proposed.