Anticoccidials

The FDA first approved use of a polyether ionophore as a feed additive for catde ia 1975. Ionophores were first isolated from bacteria generally of the Streptomjces genus, but are produced commercially by bacterial fermentation (qv). Monensia [17090-79-8] and other ionophores are being fed to over 90% of feedlot cattle grown for beef (53) to enhance efficiency of gain improvements of 5—10% are common. Ionophores also are used as anticoccidial dmgs ia poultry production and have similar, but lesser, effects ia mminants (54). 

Polyethers. Antibiotics within this family contain a number of cycHc ether and ketal units and have a carboxyHc acid group. They form complexes with mono- and divalent cations that ate soluble ia aoapolar organic solvents. They iateract with bacterial cell membranes and allow cations to pass through the membranes causiag cell death. Because of this property they have been classified as ionophores. Monensia, lasalocid, and maduramicia are examples of polyethers that are used commercially as anticoccidial agents ia poultry and as growth promotants ia mmiaants. 

Coccidiosis is a proto2oal disease of the intestinal tract of animals that leads to severe loss of productivity and death. The development and widespread use of anticoccidials has revolutionized the poultry industry. The estimated world market for anticoccidial agents in 1989 was 425 million and this was dominated by the polyether ionophore antibiotics monensin, salinomycin [53003-10-4], n imsm [55134-13-9], la.s9locid, and maduramicin [84878-61-5] (26). 

The polyether antibiotics were first recognized as a separate class with the pubHcation of the structure of monensia ia 1967 (1). Several members of the group have siace found commercial appHcation as anticoccidials ia poultry farming and ia improvement of feed efficiency for mmiaants (see Feeds and FEED additives). 

The C-30 skeleton group accounts for about 60% of the polyethers for which stmctures have been deterrnined. Most of these contain a sugar moiety, usually 2,3,6-trideoxy-4-0-methyl-D-erythto pyranose [65104-53-2]. The single spiroketal subset is ikustrated by two closely related compounds, semduramicin (4, R = H, R =) and maduramicin alpha (4, R = CH3, R = ). Maduramicin is marketed as an anticoccidial and semduramicin is under development for the same appHcation. 

The polyether antibiotics exhibit a broad range of biological, antibacterial, antifungal, antiviral, anticoccidial, antiparasitic, and insecticidal activities. They improve feed efficiency and growth performance in mminant and monogastric animals. Only the anticoccidial activity in poultry and catde, and the effect on feed efficiency in mminants such as catde and sheep are of commercial interest. 

Anticoccidial Activity. The 1968 report that claimed monensin has activity against Eimeria sp., particularly E. tenella E. macdma., and E. acervulina greatly altered the prevention and control of coccidiosis in poultry (172). It is estimated that the polyether ionophores presently constitute more than 80% of the total worldwide usage of anticoccidials (173). Lasalocid and monensin have been approved for use in control of coccidiosis in cattle. 

Table 3 Hsts the polyether antibiotics used as poultry anticoccidial dmgs in the United States. Recendy, lasalocid and monensin have been approved for use in bovine coccidiosis at levels in feed of 11—33 g/t.

Table 3. Poultry Anticoccidial Agents used in the United States...

In 1967 Agtarap et al. disclosed the isolation and structure of monensic acid (1).3 Compound 1, now known as monensin, is produced by a strain of Streptomyces cinamonensis, and exhibits broad-spectrum anticoccidial activity. Since its introduction on the market in 1971, monensin has been used very successfully to combat coccidial infections in poultry and as an additive in cattle feed.4 In the polyether family, monensin occupies a position of some historical significance. Although monensin was the fifth polyether... 

J. W. McFarland, Comparative Molecular Field Analysis (CoMFA) of anticoccidial triazines. J. Med. Chem., 35 (1992) 2543-2550. 

Replacement of one of the ethereal oxygen atoms by a methylene group is compatible with anticoccidial activity. For example, condensation of substituted aniline 35 with dimethyl ethoxymethylenemalonate affords aminoacrylate 36. Thermal cyclization in diphenyl ether gives neguinate (37).11... 

Anticoccidial activity, of polyether antibiotics, 20 135-136 Anticoccidials, 20 135—136 Anticorrosion agents, molybdenum compounds in, 17 39 Anticorrosion coatings, organic titanium compounds in, 25 134 Anti-corrosion metallic coatings, 1 713-714 Anticorrosion pigments, 19 411 Antidegradants... 

Among the aminomethylenemalonates, the A-aryl and A-hetaryl derivatives and their cyclization products are of great importance in organic chemistry, as some of them are key intermediates in the synthesis of different 4-aminoquinoline antimalarials (Scheme 1), in the preparation of anticoccidial 6,7-dialkoxy-4-hydroxyquinoline-3-carboxylates (Scheme 2), and in the production of antibacterial agents of the nalidixic acid type (Scheme 3). 

Some of these newer products are already taking an increasing share of the market. The discovery of the anticoccidial activity of monensin opened an entirely new field for the use of antibiotics in agriculture. 

Awkward Anticoccidial drugs are extensively used in the poultry industry to control infection. The polyether ionophores, such as narasin and salinomycin, are the most commonly used coccidiostats in poultry. 

Note, too, that different words are used to refer to the given information in each example coccidiostats is another way of saying anticoccidial drugs . By... 

The incompatibility of tiamulin with monensin, narasin, and salinomycin in chickens and turkeys is well documented. The toxicity of this combination in poultry may be due to interference produced by tiamulin to the metabolism of these polyether anticoccidials (257, 258). 

Tire major anticoccidial and other antiprotozoal drugs have no common chemical structure and therefore no group tests can be used to screen for residues in animal-derived foods. This is in complete contrast to the antibacterials previously discussed, which can be detected, although not identified, on the basis of their biological activity. 

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