5-Nitrofuran derivative, antibacterial

Yoneda F. and Nitta Y., Electronic structure and antibacterial activity of nitrofuran derivatives, Chem. Pharm. Bull., 12, 1264-1268, 1964. 

Smith, P.J. and Popeher, P.L.A. (2004) Quantitative structure-activity relationships from optimised ah initio bond lengths steroid binding affinity and antibacterial activity of nitrofuran derivatives. 

The 5-nitrofuran derivatives were the first nitroheterocycles of therapeutic value (Fig. 7-3). They are all synthesized from 5-nitro-2-furancarboxyaldehyde (5-nitrofurfural) or its diacetate by azomethine (Schiff base) formation with the appropriate amino compound (Eq. 7.1). The important nitrofurans in use today are shown in Figure 7-4. Since the first report of their antibacterial activity about 4,000 nitrofuran compounds have been synthesized and tested. Those that reached commercial use in human and veterinary medicine, including farm animal husbandry, did so because of their broad spectrum of activity including Gm+ and Gm- bacteria (except P. aeruginosa and some Klebsiella and Proteus strains), relatively low toxicity, and infrequent development of resistance. 

Table 6.23. Comparison of antibacterial activity of nitrofuran derivatives and antibiotics in vitro...

Matsuda, T. and Hirao, I. 1965. Antibacterial activity of 5-nitrofuran derivatives. Nippon Kagaku Zasshi 86 1195-1197. 

Furazolidone belongs to the group of nitrofurans. This antimicrobal (antibacterial and antiprotozoal) agent is used in veterinary medicine both topically and orally, particularly in animal feed. Reactions have been reported in workers exposed to it by contact with animal feed. Cross reactions with other nitrofuran derivatives are rare. 

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... 

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 AGENTSSYNTHETIC - NITROFURANS] (Vol 2) ofhydantoins [HYDANTOIN AND ITS DERIVATIVES] (Vol 13)... 

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

A number of studies in this area have been prompted by interest in the antibacterial activity of hydrazone derivatives of 5-nitrofurfuraldehyde having the general structure 33 (R1 = CH = N-NR2, R3 = R4 = H). The antibacterial activity, and associated carcinogenic and mutagenic activities, of these 2-nitrofurans are related to reduction of the nitro group, which has led to chemical studies of the reductive process (Table 5). Early work on the reduction of 2-nitrofurans has previously been reviewed (74H391). 

As early as 1940 s nitrofurans caught attention by virtue of their good antibacterial activity. Exploitation of this lead in helminth chemotherapy showed that nitroheterocycles may be useful in the treatment of various worm infections in different hosts including humans. Consequently, various laboratories set out to search for new anthelmintic drugs derived from nitroheterocycles and nitroaryls, opening one of the fascinating chapters in the chemotherapy of parasitic diseases. 

Nitrofurazone was one of the first furan derivatives to be useful as a chemotherapeutic agent. The semicarbazones of 4-nitrobenzaldehyde, 5-nitro-thiophenaldehyde, and of 5-nitropyrrolaldehyde were less effective and not suitable for clinical use . Antibacterial activity is conferred on non-nitrated furans if a nitro group is introduced in the 5-position of the furan ring. Later this was recognized to be an indispensable prerequisite. Microbiologists of the Norwich Pharmacal Co. have summarized the activity against representative species of bacteria (Table 6.22). The six tested nitrofurans, however. 

The antibacterial action of several new nitrofurans in vitro against a number of organisms has been reported by Skagius . These data indicate that 5-(5-nitro-2-furyl)-2-amino-l,3,4-thiadiazole (NF-475, ASA-140, Ph/ 778, LXXI) and its formyl derivative LXXII) have been recommended for further study in the treatment of intestinal infections of various aetiology. 

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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