Nitrofurans, list

Penicillin, the first natural antibiotic produced by genus Penicillium, discovered in 1928 by Fleming, as well as sulfonamides, the first chemotherapeutic agents discovered in the 1930s, lead a long list of currently known antibiotics. Besides 3-lactams (penicillins and cephalosporines) and sulfonamides, the list includes aminoglycosides, macrolides, tetracyclines, quinolones, peptides, polyether ionophores, ri-famycins, linkosamides, coumarins, nitrofurans, nitro heterocytes, chloramphenicol, and others. 

In view of thousands of publications that have appeared during recent years, it is difficult to summarize all aspects of the chemistry and clinical uses of nitrofurans, not to mention the wide range of experimental studies which were their necessary predecessors. In the clinical section of this chapter each drug will be described under a separate heading with emphasis on the progress in human medicine. The reader should understand in addition that the nitrofurans also have a definite place in veterinary medicine. Besides some basic work which was published soon after the compound under discussion appeared on the market, only the most recent publications have been considered. Hence, the list of references is not to be considered complete. 

For example, the original scarlet red colour changes to yellow on heating for 30 minutes at 120° and the chemical structure of the compound changes considerably (see p. 338). The bacteriostatic activity of the yellow solution against dysentery bacillus is about 250 times greater than that of panazone. This observation has prompted the synthesis of other di-(nitrofuran) derivatives, some of which are listed in Table 6.8. 

Table 6.15 lists fifty pyrimidine-containing nitrofurans of this latter type. These compounds contain a wide range of substituents at Cg and C5 of the pyrimidine ring. In addition, some compounds carry a substituent such as an alkyl group or a halogen atom on one of the carbon atoms of the butadienyl chain. 

The mechanism of antibacterial action of the furan derivatives is unknown. However, the reduced forms of nitrofurans are highly reactive and are thought to inhibit many bacterial enzyme systems, including the oxidative decarboxylation of pyruvate to acetylcoenzyme A. Nitrofurans (see list in Table 1.7) are bacteriostatic but, at high concentrations, can be bactericidal to sensitive organisms. Both chromosomal and plasmid-mediated mechanisms of resistance to nitrofurantoin occur, and these most commonly involve the inhibition of nitrofuran reductase. 

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