Nitroxoline

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Nitroxoline is an antibiotic that has been in use in Europe for about fifty years, and has proven to be very effective at combating biofilm infections. Nitroxoline was shown to cause a decrease in the biofilm density of P. aeruginosa infections, which would allow access to the infection by the immune system in vivo. It was shown that nitroxoline functions by chelating Fe and Zn ions from the biofilm matrix; when Fe and Zn were reintroduced into the system, biofilm formation activity was restored. The biofilm degradation ability is comparable to EDTA derivatives, but this drug has a history of human use in clinical settings and therefore has a precedent with which to allow its use against “slimy” biofilm infections. The chelating activities of nitroxoline have also been used in an anticancer setting. Nitroxoline has been shown to be more cytotoxic to HL60, DHL-4, PANC-1, and A2780 cells lines than clioquinol and other 8-hydroxyquinoline derivatives. It also demonstrated an increase in reactive oxygen species (ROS) production over controls, especially when Cu was added. The ROS levels reached over 350% of the controls with addition of CuCl2. The cytotoxicity production was markedly decreased with addition of ZnCl2, indicating, based on this model, that nitroxoline is not a zinc chelator. Because the zinc chelating action of clioquinol has been associated with subacute myelo-optic neuropathy, the use of nitroxoline as a cytotoxic drug in the treatment of cancers should not exhibit neurotoxic effects in humans, and in vivo trials on tumour xenografts in mice have not yielded any negative neurodegenerative effects.