Reductive metabolism and hypoxia-selective toxicity of nitracrine
Abstract The 1-nitroacridine nitracrine [NC, 1-nitro-9-(dimethylaminopropyl-amino) acridine]
is a potent hypoxia-selective cytotoxic agent in culture, but lacks activity against hypoxic
tumor cells in vivo at therapeutically accessible doses. To clarify reasons for this failure in
vivo the metabolism of NC was investigated in stirred suspension cultures of Chinese
hamster ovary cells, in EMT-6 spheroids, and in mice. One major low molecular weight
metabolite (identical to that generated by NaBH 4/Pd/C reduction) was observed in hypoxic …
is a potent hypoxia-selective cytotoxic agent in culture, but lacks activity against hypoxic
tumor cells in vivo at therapeutically accessible doses. To clarify reasons for this failure in
vivo the metabolism of NC was investigated in stirred suspension cultures of Chinese
hamster ovary cells, in EMT-6 spheroids, and in mice. One major low molecular weight
metabolite (identical to that generated by NaBH 4/Pd/C reduction) was observed in hypoxic …
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