Amphomycin

Originator

Amphocortrin CR,Warner Lambert,US,1963

Uses

Amphomycin is a lipopeptide antibiotic produced by Streptomycetes and Actinoplanes, initially reported by researchers at Bristol-Myers in 1953 from Streptomyces canus. Amphomycin was marketed as a complex of closely related analogues in the 1950s and 1960s. Structure elucidation was not completed until 2000. Amphomycin is active against Gram positive bacteria, inhibiting peptidoglycan synthesis and blocking cell wall development. Amphomycin is closely related to a number of “lost” antibiotics, aspartocin, crystallomycin, glumamycin, friulimicin, laspartocin, tsushimycin and zaomycin. Interest in amphomycin was re-awakened with the discovery of friulimicin activity against antibiotic resistant strains.

Manufacturing Process

The process for producing amphomycin comprises cultivating a strain of Streptomyces canus in an aqueous, nutrient-containing carbohydrate solution under submerged aerobic conditions until substantial antibacterial activity is imparted to the solution and then recovering the so-produced amphomycin from the fermentation broth.
The process of decolorizing solutions of amphomycin then involves treatment with activated charcoal, followed by the steps of (1) extracting the antibiotic into a water-immiscible organic solvent under strongly acid conditions or precipitating the amphomycin from aqueous solution by adjusting the pH to a point within the range of pH 3.0 to 4.0, (2) removing impurities from strongly acid, aqueous solution of amphomycin by extraction of the impurities with methyl isobutyl ketone and amyl acetate, (3) extracting the amphomycin from a strongly acid solution in butanol by the use of water having a pH higher than 4, (4) extracting the amphomycin from solution in water-immiscible organic solvent into water whose pH is greater than 6.0, (5) precipitating amphomycin from solution by formation of insoluble derivatives of the basic function, and (6) precipitating amphomycin from solution by formation of insoluble derivates of the acidic function.
The amphomycin is then converted to the calcium salt with calcium hydroxide.

Therapeutic Function

Antibiotic

Biological Activity

amphomycin is a natural antibacterial lipopeptide.cyclic lipopeptides are a promising class of natural products with antibiotic properties. cyclic lipopeptides are amphiphilic molecules, composed of a fatty acid tail linked to a short oligopeptide which form a macrocylic ring structure.

Safety Profile

Poison by intravenous andintraperitoneal routes. Moderately toxic by ingestion.Induces hemolysis. Active against gram-positive bacteria.Suggested as a topical agent for animal and plantinfections. When heated to decomposition it emits acridsmoke and

in vitro

in previous study, calf brain endoplasmic reticulum membranes were incubated with varying concentrations of gdp-mannose in the presence and absence of amphomycin, results showed no significant difference in apparent km for gdp-mannose. however, the vmax was reduced in the presence of amphomycin as compared with in its absence. moreover, when mannosylphosphoryldolichol synthase activity was measured in the presence of amphomycin, the shape of the substrate velocity curve changed from a rectangular hyperbola to a sigmoid [1].

in vivo

the pk of lipopeptides, the semi-synthetic amphomycin analogues, were evaluated in mice and rats following single i.v. and oral administration. following oral administration at 50 mg/kg, plasma concentrations of amphomycin analogues were

References

[1] d. k. banerjee. amphomycin inhibits mannosylphosphoryldolichol synthesis by forming a complex with dolichylmonophosphate. the journal of biological chemisty 264(4), 2024-2028 (1989).
[2] pasetka cj, erfle dj, cameron dr, clement jj, rubinchik e. novel antimicrobial lipopeptides with long in vivo half-lives. int j antimicrob agents. 2010 feb;35(2):182-5.

Raw materials

Preparation Products