Bifunctional Metal – Nitroimidazole Complexes for Hypoxia Theranosis in Cancer

Abstract

Oxygen supply -demand imbalances can render proliferating cells acutely or chronically hypoxic. In cancer cells, hypoxia-induced pathophysiological changes give rise to genetic changes that lead to treatment-resistant, aggressive phenotypes. The reduced curability of hypoxic tumours by radiotherapy is one of consequent challenges, but their hypoxia also offers unique, exploitable properties. Nitroimidazoles, for example, capitalize on oxygen-sensitive reductive activation to achieve hypoxia-selective localization for theranostic consequence. The discovery of 2-nitroimidazole (azomycin) heralded the development of many drugs, including effective radiosensitizers of hypoxic cells. These electron-affinic, reductively bioactivated nitroheterocyclics undergo initial oxygen-reversible, enzymatic one-electron reductions that lead to the formation of molecular adducts that impair vital