Nitrofurans, use

Chemically it is nitrofuran, used for American trypanosomiasis which is commonly known as Chagas disease. After oral administration, it is well absorbed and plasma half life is about three hours. 

Nitrovin (Fig. 6.4) is a nitrofuran used as a growth promoter in animal feeds for chickens, turkeys, swine, and calves at concentrations varying from 10 to 40 ppm in tlie feed. The compound has been withdrawn in the European Union. 

As described above, the nitrofurans used in veterinary practice are quickly metabolized by the animal. 

Chemically synthesized antimicrobials used in animal and poultry feeds include arsenicals, eg, arsanilic acid [98-50-0] sodium arsanilate [127-85-5] and roxarsone [121-19-7]-, sulfa dmgs, eg, sulfadimethoxine [122-11-2], sulfamethazine [57-68-1], and sulfathiazole [72-14-0]-, carbadox [6804-07-5]-, and nitrofurans, eg, furazoHdone [67 5-8] and nitrofurazone [59-87-0] (see Antibacterial agents, synthetic Antiparasitic agents). 

Although in vitro mutagenicity tests suggest that some nitrofurans in general provoke a positive response, use of in vivo mammalian systems has produced equivocal or negative results. 

These three nitrofurans have been used therapeutically for over 30 years with no reports of human neoplasia and the relevance of the animal findings to short term therapy in humans has not been estabUshed. 

The nitrofuran group of drugs (Fig. 5.18) is based on the finding over 40 years ago that a nitro group in the 5 position of 2-substituted furans endowed these eompounds with antibacterial activity. Many hundreds of such compounds have been synthesized, but only a few are in current therapeutic use. In the most important nitrofurans, an azomethine group, —CH=N—, is attached at C-2 and a nitro group at C-5. Less "important nitrofurans have a vinyl group, —CH=CH—, at C-2. 

N-Aminoimidazolinones have found extensive use as synthons for such nitrofurans. Reaction of an appropriate 1,2-diamine (27, 31) with urea gives the desired heterocycle (28, 32). Nitrosation with... 

While nitrofurans are often prepared as antibacterial agents, nitroimidazole forms the basis for an extensive class of agents used in the treatment of infections by the protozoans. Unlike bacterial infections, protozoal infections are seldom life-threatening. The physical discomfort occasioned by such infections is, however, of sufficient importance to provide a useful therapeutic place for antiprotozoal agents. A particularly common set of such conditions are parasitic infections of the genitalia caused by Trichomonas vaginalis. These disorders are called trichomoniasis. 

Dicarbonyl compounds can be converted into furans by methods other than the classical Feist- Benary method, the essential feature of which is alkylation by a haloketone or similar species. A curious variation is provided by the use of trichloronitroethene, Cl2C=CCIN02, which condenses with two moles of a 1,3-dicarbonyl compound by Michael addition followed by elimination of two chloride ions the third chloride is lost at the aroma-tization step so that, for example, methyl 3-oxobenzenepropanoate is converted into the nitrofuran 38."... 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

As noted above, nitrofurans and nitroimidazoles have proven useful moieties for the preparation of antibacterial and antiprotozoal agents. It is thus of note that nitrothiazoles have also been used successfully in the preparation of antiparasitic agents. Condensation of 6-nitro-2-aminothiazole (194, available from nitration of aminothiazole) with ethylisocyanate yields the antiprotozoal agent... 

A number of 5-nitro-2-furaldehyde derivatives, called nitrofurans, are used in the treatment and/or prophylaxis of microbial infections, primarily in the urinary tract. Recent evidence suggests that the reduction of the 5-nitro group to the nitro anion results in bacterial toxicity. Intermediate metabolites modify various bacterial macromolecules that affect a variety of biochemical processes (e.g., DNA and RNA synthesis, protein synthesis) this observation may explain the lack of resistance development to these drugs. Evidence also indicates that the nitro anion undergoes recycling with the production of superoxide and other toxic oxygen compounds. It is presumed that the nitrofurans are selectively toxic to microbial cells because in humans, the slower reduction by mammalian cells prevents high serum concentrations. 

In order to achieve 2-nitration, acetyl nitrate may be used as the reagent, but unlike pyrrole a semi-stable adduct, 5-acetoxy-2,5-dihydro-2-nitrofuran, is formed as an intermediate product (Scheme 6.22). This eliminates acetic acid when treated with pyridine. Furan also undergoes initial bromination or chlorination (X = Br or Cl) in ethanol at -40 °C, but then addition of two ethoxyl units occurs with the expulsion of halide ion (Scheme 6.23). 

Among fluoroquinolones, ofloxacin, pefloxacin and sparfloxacin can be used in alternative regimen, when drugs like rifampicin can not be used. Detailed pharmacology of quinolones is discussed in chapter Sulfonamides, nitrofurans and quinolones. ... 

The nitrofurans are synthetic antibacterial compounds, all containing in their molecule a characteristic 5-nitrofuran ring (Fig. 3.5). Furazolidone, nitrofurazone, furaltadone, and nitrofurantoin are all nitrofiirans that have been widely used in the prophylactic and therapeutic treatment of infections caused by bacteria and protozoa in swine, cattle, poultry, rabbits, and fish. They have been also used as feed additives in animal husbandry. They are very effective drugs and do not appreciably contribute to the development of resistance (120). 

Besides -lactams and streptomycin, many other drugs including sulfonamides, and to a lesser extent neomycin, nitrofurans, erythromycin, spiramycin, novobiocin, and the tetracyclines, are known to cause allergic reactions in sensitive persons (80, 91). However, such reactions in humans arc variable and are mostly related to therapeutic use. 

In addition, specific testing was performed for chloramphenicol in muscle, nitrofurans in muscle and serum, dimefridazole in muscle of pigs and poultry, and sulfonamides in liver. In Australia, chloramphenicol is not registered for use in food animals and nitrofurans are only available as a topical preparation for use in companion animals. No residues of either of these compounds were detected. No residues of dimefridazole were detected in pig and poultry samples. Sulfonamide residues were monitored in cattle and pigs. No residues were detected in 613 cattle samples. In 594 pig liver samples analyzed, 9 residues of sulfamethazine (sulfamethazine) were detected, 4 of which were above the MRL. 

On the other hand, the type of the packaging material did not exert any effect on tire residue levels at a storage temperature of 20 C. At 4 C, nitrofuran residues remained stable when the egg samples were stored in glass or polypropylene tubes, but a loss of 60-70% was observed when a laminated foil was used. At 20 C, all four nitrofurans exhibited marked residue reduction, the losses being 30-50% for glass tubes, 40-60% for polypropylene tubes, and 100% for laminated foil. 

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