Redox systems as conduits for antimalarial compounds
Joshua Howarth · Journal of Antimicrobial Chemotherapy · 2001
Sir, At the turn of the nineteenth century, Ehrlich focused on the selective staining of malaria-infected cells over non-infected cells, with methylene blue and acridine orange.1 On reviewing this information, two simple questions arose: why do these compounds selectively target parasite infected cells and can this information be used against the parasite? We propose the following: methylene blue is a cationic redox dye, and on examination of the physiological consequences of malarial infection, we can see why this compound has a high affinity for infected blood cells. Infected cells are under a high degree of endogenous oxidant stress stemming from the parasitic presence, and various physiological processes come into play to relieve this stress, primarily through provision of substrates for reduction in a process known as the hexose monophosphate shunt (HMS). Therefore, the introduction of an alternative reductive target into the system, here a redox dye, will prompt the uptake of this target by the infected cell.2 We decided to investigate this hypothesis and chose to utilize these cationic redox dyes to show that they could operate as infection-specific conduits for other antimalarial compounds.