Efficient redox cycling of nitroquinoline bioreductive drugs due to aerobic nitroreduction in Chinese hamster cells

摘要: Abstract Nitroquinoline bioreductive drugs with 4-alkylamino substituents undergo one-electron reduction in mammalian cells, resulting futile redox cycling due to oxidation of the nitro radical anion aerobic cultures, and eventual corresponding amines absence oxygen. Rates drug-induced oxygen consumption (R) cyanide-treated AA8 cell cultures were determined for 17 nitroquinolines. There was a linear dependence log R on potential at pH 7 (E 1 ) slope 7.1 V −1 , excluding compounds ortho group. The latter had anomalously low rates relative E suggesting that interaction active site nitroreductases is impeded sterically such compounds. Absolute values (and observed dependence) well predicted by simple kinetic model used net nitroreduction under anoxia as measure cells. This indicates 4-alkylaminonitroquinolines occurs high efficiency there are no quantitatively significant fates anions cells other than their reaction (or spontaneous disproportionation hypoxia).