Nitrofurans: mode of action
Gounot, A.M.; Brevet, C.; Videz, S.
Annales Pharmaceutiques Francaises 37(9-10): 421-428
1979
ISSN/ISBN: 0003-4509 PMID: 94981 Document Number: 144590
This bibliographic review updates current knowledge concerning the mode of action of nitrofurans at the cellular level. The antibacterial properties of nitrofurans are principally attributed to the presence of the .sbd.NO2 group which must be reduced by cellular enzymes to be activated. Two reductases were isolated from Escherichia coli, one (I) being activated in aerobiosis, the other (II) in anaerobiosis. Mutants lacking type I reductase become resistant to nitrofurans. This resistance may be chromosomal, but it is also possible that the antibacterial property could occur without nitrofuran reduction or by other groups. Reduced nitrofuran acts by direct interference with the electron transport system and by reacting with cellular macromolecules. The most important effects of nitrofurans occur at the DNA level: cuts, mutations, binding to the DNA molecule blocking replication and transcription. In addition to the inhibition of RNA synthesis and therefore of protein synthesis, there is direct action upon ribosomes and proteins. Growth is consequently inhibited. At sublethal doses, inhibition is temporary and induces cellular filamentation. The effects of nitrofurans on energy metabolism are difficult to interpret.