Targeting the cancer stem cell (CSC) metabolism with designed, reactive metal complexes

ended

Designed, bulky metal complexes with a labile coordination position react with accessible guanines at G4 DNA quadruplexes, promoting changes in their conformation and function. Importantly, we have found that this selective reactivity leads to very interesting biological effects. In particular, some of these compounds are able to suppress the “stem”-like character of cancer stem cells, apparently by deterring their mitochondrial respiration. Preliminary experiments, including in vivo assays, confirm that these biological effects result in remarkable antitumoral activities. This proposal aims to explore the scope of the approach, confirm that the mechanism of action involves mitochondria, design more selective versions and exploit the potential of the compounds as new type of anticancer agents.