Anticoccidials monensin

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). 

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.

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... 

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. 

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). 

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

Polyelkers. Antibiotics within this family contain a number of cyclic ether and ketal units and have a carboxylic acid group. They form complexes with mono- and divalent cations that arc soluble in nonpolar organic solvents. They interact with bacterial cell membranes and allow cations to pass through the membranes causing cell death. Because of this property they have been classified as ionophores. Monensin, lasalocid, and maduramicin are examples of polyethers that are used commercially as anticoccidial agents in poultry and as growth promotants in ruminants. 

ANTIBIOTICS POLYETHERS. The polvether antibiotics were first recognized as a separate class with the publication of the structure of monensin in 1967. Several members of the group have since found commercial application as anticoccidials in poultry farming and in improvement of feed efficiency for ruminants. 

Ionophores, or polyether (PET) antibiotics, produced by various species of Streptomyces, possess broad spectrum anticoccidial activities. They are chemically characterized by several cyclic esters, a single terminal carboxylic acid group, and several hydroxyl groups. Representative members of this class include salinomycin (SAL), monensin (MON), lasalocid (LAS), narasin (NAR), maduramicin (MAD), and semduramicin (SEM). The main chemical properties of interest in the extraction methodology are their low polarities and instability under acidic conditions. They are able to form stable complexes with alkaline cations. All of these compounds, with the exception of LAS, bind monovalent cations (e.g., Na+ and K+). Lasalocid has a tendency to form dimers and can form complexes with divalent cations such as Mg2+ and Ca2+. The formation of metal complexes results in all of these compounds adopting a quasi-cyclic formation consequent to head-to-tail hydrogen bonding. No MRLs have yet been set by the EU for any of the carboxylic acid PETs (98). 

Figure 2 Examples of polyketides. Polyketides demonstrate a broad range of biological activities, including antibiotic (oxytetracycline and erythromycin), antitumor (doxorubicin and dynemicin), antiparasitic (avermectin), and immunosuppressive (FK506). Monensin is used as a bovine feed supplement and an anticoccidial agent.

Even more complex is the structure of monensin, a compound which has been extensively used as an anticoccidial agent for poultry and shown to improve the efficiency of feed utilization in ruminant animals. When submitted to a culture of Sebekia bevihana, monensin was first quantitatively converted by enzymatic reduction of the 8-hydroxy-ketone (which is in equilibrium with its hemiketal tautomeric form) and was regioselectively further hydroxylated at the C-29 methyl group as well as at the nearby ethyl group substituent[94). 

Polyether lonophores. Isolation and identification of antibiotic X-14885A was reported.Its structure is closely related to A-23187 and cezomycin, members of the pyrrolether class of natural ionophores. Aspects of the discovery and ionophoric properties of the X-14868 complex were described. Another new naturally derived agent, CP-53607 (32), was reported to be effective t ainst coccidia and as a rumen propionic acid stimulant. The C-26 urethane analogs of monensin transported both Rb and Ca. Their antibacterial and anticoccidial activities were also reported as greater than monensin. Microbial conversion of grisorixin by Streptomyces rimosus was found to produce an inactive and detoxified product. A unified stereochemical model of polyether antibiotic structure and biogenesis was proposed. Ibtal synthesis of ionophores continued to be of interest and the unnatural enantiomer of lasalocid A was found to have similar biolc cal properties to the natural product. ... 

Monensin S. cinnamonensis Membrane (ionophore) Anticoccidial, growth promotant... 

Other veterinary drugs Other veterinary drugs of importance are the anticoccidial feed additives such as the ionophores, narasin, monensin, salinomycin, apramycin, lasalocid, and nicarbazin. The USDA/ FSIS have a method for the major ionophores in tissue samples, which is based on purification of sample extracts by silica gel, alumina, or ion-ex-change column chromatography and determination by TEC with detection by bioautography. A number of alternative methods based on immunoassays, biosensor technology, and HPLC have been developed. 

H. D. Chapman and J. Sandstrom, and S. W. Breeding, Effect of the anticoccidial agents halofuginone and monensin when given with growth promoting antibiotics upon the control of coccidiosis in the turkey. Avian Pathol, 1998, 27, 498-504. 

Monensin, a compound produced by Streptomyces cinnamonensis. is an inhibitor of alkali metal cation transport into rat liver mlto ondria and is claimed to have broad spectrum anticoccidial activity. The complete structure was determined by x-ray analysis of the silver salt. 

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