The presence of hypoxic cells in human solid tumours is one of the causes of tumour resistance to conventional
therapy, and is also associated with processes that promote the tumour progression. Different chemical agents have been designed in order to take advantage of the particular metabolic characteristics of hypoxic regions. These drugs, called bioreductive agents, are activated inside the hypoxic cells to give active species that, in the presence of
oxygen, are oxidised back to the non-toxic parent compound. Several
quinoxaline 1,4-di-N-oxides have been described as potential bioreductive agents, and among them, 7-cloro-3-[[(N,N-dimethylamino)propy]amino]-2-quinoxalinecarbonitrile 1,4-di-N-oxide hydrocloride (Q-85 HCl) appeared to be the most promising one. In the present work, the selective cytotoxicity of
Q-85 HCl was studied in several human tumour cell lines of different origin (Caco2, MCF-7, HT-29 and Tk-10). Cell viability was calculated after 2 h treatment under hypoxic and well-oxygenated conditions. The potency (the concentration that gives 1% of cell survival) in
hypoxia and
hypoxia cytotoxicity ratio (HCR = potency in oxygenated conditions/potency in
hypoxia) were calculated after a 14-day clonogenic assay.
Q-85 HCl was more toxic in
hypoxia than in well-oxygenated cells in all the tumour cell lines. The best profile of potency in
hypoxia (0.4 micromol/L) and selectivity (HCR=155) was found in CaCo-2 cells. Altogether, these results suggest an in vitro
biological profile for
Q-85 HCl that makes it an interesting candidate for the development as a bioreductive agent.