Oxygen-deprived cells, reduction

Bioprecursors provide relevant examples of chemotherapeutic agents whose activation occurs by reduction in oxygen-deprived cells. Bioprecursors certainly appear as a viable class of prodrugs, since they avoid potential toxicity problems caused by the carrier moiety (see below). In contrast, attention must be given here to metabolic intermediates. 

Hypoxia is a deficiency of oxygen needed to maintain cellular homeostasis. It may be caused by a reduction in blood supply, namely ischemia, decreased cardiopulmonary function, and diminished oxygen-carrying capacity of the blood. Subsequent oxygen deficiency in tissues leads to depressed aerobic metabolism and, thus, insufficient ATP synthesis. Reductions in blood flow also exacerbate oxygen deprivation by impairing delivery of nutrients, such as glucose, and the removal of metabolic wastes, such as C02, from affected cells. 

Antitumor agents mitomycin A (61 A) and mitomycin C (61C) contain a latent quinone functionality, which is exposed by reductive activation and elimination of a glycoside or an alcohol followed by opening of the aziridine ring. These quinone methides then react with nucleic acids to form bis-adducts.103 The reductive activation of mitomycins provides selectivity in targeting solid tumors, because this is favored in the oxygen-deprived environment of tumor cells, and inhibited by the oxygen-rich environment of healthy tissues.107... 

When cells of higher plants are under anaerobic conditions (deprived of oxygen) carbon dioxide release persists for some time and at least part of this carbon dioxide arises from a type of anaerobic respiration known as fermentation in which the electrons and protons are transferred to organic compounds such as pyruvic acid and acetaldehyde. The reduction of these compounds results in the appearance in the cell of compounds like lactic acid and ethanol. Clearly, this fermentation which can occur in the cells of higher plants closely resembles the alcoholic fermentation of yeast first studied in detail by Pasteur in 1870 and the production of lactic acid in manunalian muscles under conditions of an oxygen deficit, a process studied in detail by Fletcher and Hopkins in 1907. 

---