Correlation between metabolic reduction rates and electron affinity of nitroheterocycles.

摘要: Abstract Nitroheterocyclic compounds can selectively sensitize hypoxic (tumor) cells to radiation damage in vitro . However, results vivo have generally been less optimistic, inasmuch as metabolic reduction of these drugs not only limits effective lifetime but also produces intermediates with marked cytotoxic and carcinogenic activity. With three reducing systems vitro, E. coli B/r, mouse L-929 cells, liver microsomes, the rate nitroreduction several nitroheterocycles was found be proportional their electron affinity (half-wave potential). Relative nitrofurazone each system, metronidazole (Flagyl), N -hydroxyethyl-3,5-dinitropyrrole, misonidazole, nifuroxime, nitrofurantoin, furylfuramide were metabolized about 200, 20, 2, 1.4, 1.2 times rapidly, while 3,5-dinitrobenzonitrile, 2,5-dinitrophenol, 5-nitro-2-furaldehyde diacetate reduced 3, 4 more rapidly. Since has previously correlated subsequent cytotoxicity, DNA damage, mutagenicity, present suggest that improvements therapeutic efficacy ( i.e. , sensitization without toxicity carcinogenicity) will dependent on development appropriate pharmacological properties.