The Design of Gold-Based, Mitochondria-Targeted Chemotherapeutics
Recent developments in understanding the central place of mitochondria as regulators of programmed cell death have stimulated enormous interest in using them as targets for cancer chemotherapy. To overcome drug resistance and the lack of selectivity of cancer drugs in differentiating between normal and tumour cells, many strategies have been described in recent literature, including the use of delocalized lipophilic cations that selectively accumulate in tumour-cell mitochondria. Thioredoxin reductase, an enzyme involved in redox regulation and cell growth, has also emerged recently as an attractive drug target. Here we discuss the rationale for the design of lipophilic, cationic Au(i) phosphine complexes that are targeted to mitochondria of tumour cells and have potent and selective anticancer activity for cancer cells but not for normal cells. Our discovery that the thioredoxin system may be a critical target responsible for the selective toxicity provides a new strategy in the development of mitochondria-targeted chemotherapeutics.
Australian Journal of Chemistry
Inorganic Chemistry not elsewhere classified