Antibiotics monensin

Marecek and colleagues developed a new electrochemical method for the rapid quantitative analysis of the antibiotic monensin in the fermentation vats used during its production. The standard method for the analysis, which is based on a test for microbiological activity, is both difficult and time-consuming. As part of the study, samples taken at different times from a fermentation production vat were analyzed for the concentration of monensin using both the electrochemical and microbiological procedures. The results, in parts per thousand (ppt), are reported in the following table. 

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 mechanism of inhibition has not been characterized, but it is probably related to the ionophoretic properties of these antibiotics. Monensin has been shown to inhibit the intracellular transport of viral membrane proteins of cells infected with Semliki Forest vims (169). The formation of syncytia, normally observed when T-lymphoblastoid cell line (CEM) cells are cocultivated with human immunodeficiency vims (HlV-l)-infected T-ceU leukemia cell line (MOLT-3) cells, was significantly inhibited in the presence of monensin (170). This observation suggests that the viral glycoproteins in the treated cells were not transported to the cell surface from the Golgi membrane. 

Reaction mechanism. The antibiotic monensin (Mon) is a linear monocarboxylic acid. In its anionic form it binds very tightly to monovalent cations. For Na+ +Mon = NaMon,... 

Three broad groupings, of the antibiotic substances presently used in animal production, include (a) broad-spectrum antibiotics, including penicillins and tetracyclines, which are effective against a wide variety of pathogenic and non-pathogenic bacteria (b) several narrow-spectrum antibiotics that are not used in human medicine and. (c) the ionophore antibiotics, monensin. lasalocid and salinomycin Monensin and lasalocid are used as rumen fermentation regulators in beef cattle, and the three ionophores are used as coccidiostats in poultry production. The ionophores. which are not used in human medicine, were first introduced in the 1970 s and account for most of the increase in antibiotic usage in animal production since the 1960 s. 

The most widely used and researched growth promotant of this type is the polyether antibiotic monensin (63). Monensin, at levels of 33 p.p.m. in feed, has been shown to increase efficiency of feed utilization in both sheep and cattle fed a variety of rations by up to 12%. Slaughter and carcass analysis data indicate that the main effect of the compound is to increase the efficiency of dietary energy retention in the carcass. Its mode of action is thought to be related to its ability to increase the molar proportion of propionate, at the expense of acetate and butyrate, produced in rumen fermentation probably by an effect on the relative microfloral populations. Theoretically this should make more energy available to the animal. 

Because the stability constant of its complex with potassium is much greater than that with sodium, valinomycin is a relatively specific potassium ionophore. In contrast, the mushroom peptide antamanide has a binding cavity of a different geometry and shows a strong preference for sodium ions.388,390 The structure of the Na+-antamanide complex is also shown in Fig. 8-22B. The Streptomyces polyether antibiotic monensin (Fig. 8-22D),389,391 a popular additive to animal feeds, is also an ionophore. However, its mode of action, which involves disruption of Golgi functions, is uncertain 392... 

Alkynelester coupling.1 A key step in a synthesis of the antibiotic monensin (4) involves coupling of an alkyne (2), derived from a degradation product of the... 

Quantification of five different drugs in pigs kidney Separation of carboxylic polyether antibiotics (monensin, salinomycin, and narasin) with an amino bonded phase and 15% methanol in carbon dioxide using light-scattering detector Analysis of hydroxylated metabolites of dialkyldithio-carbamates... 

Y., Staunton, J. and Leadlay, P.F. (2003) Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization. Molecular Microbiology. 49,1179-1190. 

Bromoetherification, the addition of the elements of Br and OR to a double bond, is a common method for constructing rings containing oxygen atoms. This reaction has been used in the synthesis of the polyether antibiotic monensin (Problem 21.40). Draw a stepwise mechanism for the following intramolecular bromoetherification reaction. 

Systematic studies on the chelation-controlled additions were carried out, varying the type of alkoxy group, the carbon nucleophile, the solvent and the temperature. It was found that a-alkoxy ketones react highly stereoselectively with Grignard reagents in THF (equation 24). Alkyllithiums were not effec-tive. -6 The generalization was made use of in the synthesis of the polyether antibiotic monensin. ... 

The step boxed in yellow in the ester reduction scheme on p. 000 gave an aldehyde. The aldehyde is more readily reduced than the ester, so the reduction doesn t stop there, but carries on to the alcohol oxidation level. How, then, can you reduce an ester to an aldehyde This is a real problem in synthetic chemistry—the ester below, for example, is easy to make by methods you will meet in Chapter 27. But an important synthesis of the antibiotic monensin requires the aldehyde. 

Figure 5. Dot Blot Quantitation. Arrows mark the addition to, and removal from, the feed of the ionophore antibiotic monensin. Points correspond to normalized daily values. The profiles are drawn from a running three day average of the daily values (see text for discussion). (Reproduced with permission from Ref. 14. Copyright 1988 American Society for Microbiology)...

The conformational studies on the ferrichromes and on ferrioxamine B indicate that a number of intramolecular hydrogen bonds are formed in the process of metal-chelation and that these contribute to the overall stability of the coordinated conformation relative to that of the free species. Consistent with this view, it should be mentioned that extensive hydrogen bonding has also been observed in the low molecular weight monovalent cation complexes of the antibiotics monensin, nigericin, dianemycin, the enniatins and valinomycin by NMR spectroscopy (69, 70), X-ray crystallography (71, 72, 73), or both. Like the siderochromes, these compounds act by mediating cation fluxes across membranes. 

As a final remark on podands, we should mention one innovation. Tsukube et al. proposed [114—117 a novel general approach of chemical modification of natural podands, i.e., the polyether antibiotics monensine. 

The ionophore antibiotic monensin complexed with a sodium cation. 

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