Medicinal Inorganic Chemistry: Using Toxicity to Advantage

Abstract

AbstractThe field of metal‐based compounds intended for treatment of cancer has long been dominated by cisplatin, first approved for clinical use in treating testicular cancer, in 1978. By all accounts, cisplatin has been a resounding success. Other platinum‐based compounds have been introduced since then, with carboplatin and oxaliplatin serving to broaden the range of tumors that can be effectively treated. Overcoming tumor cell resistance is an ongoing problem, and the target of many newer platinum‐based anticancer therapeutic agents. More recently, substitution of platinum with other metal ions, such as ruthenium, gallium, lanthanides, and arsenic, has expanded the array of potential metal‐based anticancer agents, with the arsenic trioxide having particular success against acute promyelocytic leukemia (APL).A key feature of metal‐based anticancer therapeutic agents is that they are toxic by design: without toxicity, the tumor cells could not be eliminated. Similar strategies are useful for diseases such as malaria, Chagas disease, and leishmaniasis, in which the target organisms are parasites. For parasitic diseases, as well as for resistant bacterial infections, or to stop tumor growth, the requirement for appropriate metallotherapeutic design is to minimize contact with healthy tissue, to target particular cells, and to avoid premature release of the metal ion.