Nitrofuran Antibacterials

Nitrotoluenes including 2,4,6-trinitrotoluene (TNT) are important components of explosives and several nitroarenes including the antibacterial nitrofurans have established mntagenicity (Purohit and Basu 2000). Substantial effort has been directed to the degradation of nitroarenes, and to their reduction to amines. Although nitroarene reductases, noted in Chapter 3, Part 3, are distribnted in a range of biota, the products may not necessarily represent intermediates in the degradation... 

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). 

The nitrofurans encompass a class of synthetic antibacterials characterized by the 5-nitro-2-furanyl group ... 

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. 

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. 

The nitrofurans and sulfa drugs are antibacterial feed additives that... 

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... 

Virtually all dmgs that contain a furan ring involve starting materials in which the ring is preformed. A sizeable number of antibacterial agents were at one time available that were based on relatively simple derivatives of 5-nitrofuran. These have greatly... 

Condensation of anthrandic acid (77-1) with an iminoether represents another method for preparing quinazolones. The reaction with the iminoether (77-2) from 2-cyano-5-nitrofuran and ethanohc acid can be visualized as proceeding through the formation of the amidine from addition-elimination of anthranilic acid cycliza-tion then affords the observed product (77-3). This is then converted to chloride (77-4) in the usual way. Displacement of the newly introduced chlorine with diethanolamine leads to the formation of nifurquinazol (77-5) [86], one of the antibacterial nitrofmans (see Chapter 8). 

The arsenal of antibacterials available for the treatment of infectious diseases has expanded exponentially since then. Currently, as illustrated in Fig. 1, the repertoire includes the (J-lactams (e.g. 3) sulfa drugs (e.g. 4) macrolides (e.g. 5, erythromycin A), nitrofuran drugs (e.g. 6, furazolidone), and many aminoglycosides. 

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). 

Nitrofuran antibacterials are synthetic compounds that are substitution products of the 5-nitrofuran nucleus, differing in the substituent at position 2. This substituent may be an azomethine group connected with other ring systems, or an alkyl, acyl, hydroxyalkyl, or carboxyl group, free or esterified. All these antibacterials are susceptible to photolysis, particularly by sunlight, and manipulations must be carried out under subdued light. 

Extraction of nitrofuran antibacterials from edible animal products should render the bound residues soluble, remove most if not all of tire proteins, and provide high yields for ah analytes. Sample extraction/deproteinization is usually accomplished with organic solvents capable to free the noncovalently bound residues from the endogenous macromolecules. Organic solvents including acetoni-... 

Table 29.5 Physicochemical Methods for Nitrofuran Antibacterials in Edible Animal Products... 

In liquid chromatographic analysis of nitrofuran antibacterials, the most popular detector is the ultraviolet visible (UV-vis) spectrophotometer. Nitrofurans exhibit strong absorption at wavelengths around 365 nm and are, therefore, ideal for direct determination (Table 29.5). Detection wavelengths of 275 nm (56, 57) and 400 nm (175) have also been suggested. Electrochemical detection is also frequently applied in liquid chromatographic methods for the determination of various nitrofuran antibacterials in edible animal products (172, 173, 179). 

The majority of these are antibiotics and they cover a diverse group including the glycopeptide, avoparcin (95), tetracycline, macrolides, such as tylosin (23) and virginiamycin (96), as well as peptides, glycopeptides and terpenes. Antibacterials such as the quinoxaline-1,4-dioxide, carbadox (39), and nitrofurans, e.g. furazolidone (35) and nitrovin (97), are also represented. 

In the group of synthetic benzofurans are found nitro derivatives with the nitro group on the benzofuran ring.36-38 It is difficult to attribute these properties to a definite toxophore, isopropyl derivatives being at least as active as nitro derivatives. Nitrobenzofurans are also bactericidal.39,40 A parallel between structure and antibacterial activity has been made in the nitrofuran series.41... 

ANTIBACTERIAL AGENTSSYNTFIETIC - NITROFURANS] (Vol 2) 2-Acetoxy-9,10-dimethoxyl,3,4,6,7,llb-hexahydro-2Hbenzo[a]quinolizm-3-carboxylic acid diethylamide [63-12-7]... 

Furan derivatives - [ANTIBACTERIAL AGENTS SYNTHETIC - NITROFURANS] (Vol 2) - [FURANDERIVATIVES] (Supplement) -resmintermediates [FURANDERIVATIVES] (Supplement) -as solvents [FURANDERIVATIVES] (Supplement) -synthetic rubber modifiers [FURANDERIVATIVES] (Supplement)... 

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