Polyene antibiotics amphotericin

Some substances form pores in the membrane that do not exhibit ion selectivity and permit flow of the solution through the membrane. These include the polyene antibiotics amphotericin B,... 

The mixing of nematogenic compounds with chiral solutes has been shown to lead to cholesteric phases without any chemical interactions.147 Milhaud and Michels describe the interactions of multilamellar vesicles formed from dilauryl-phosphotidylcholine (DLPC) with chiral polyene antibiotics amphotericin B (amB) and nystatin (Ny).148 Even at low concentrations of antibiotic (molar ratio of DLPC to antibiotic >130) twisted ribbons are seen to form just as the CD signals start to strengthen. The results support the concept that chiral solutes can induce chiral order in these lyotropic liquid crystalline systems and are consistent with the observations for thermotropic liquid crystal systems. Clearly the lipid membrane can be chirally influenced by the addition of appropriate solutes. 

Bolard J, Seigneuret M, Boudet G. Interaction between phospholipid bilayer membranes and the polyene antibiotic amphotericin B lipid state and cholesterol content dependence. Biochim Biophys Acta 1980 599 280. 

The polyene antibiotics, amphotericin B and nystatin, are of bacterial origin. They insert themselves into fun-LiJIlmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Amphotericin B is available in the form of sterile lyophilized powder. Because it is insoluble in water, it is marketed with sodium deoxycholate for dispersal in sterile water and 5% dextrose. The polyene antibiotics — amphotericin B, nystatin, and candicidin — are all poorly absorbed from the gastrointestinal tract. In the plasma, amphotericin B binds to lipoproteins including cholesterol. It is extensively metabolized and the inactive metabolite, or metabolites, are slowly excreted in the urine. 

Vertut-Croquin A, Bolard J, Chabbert M, Gary-Bobo C. Differences in the interaction of the polyene antibiotic amphotericin B with cholesterol- or ergosterol-containing phospholipid vesicles. A circular dichroism and permeability study. Biochemistry 1983 22(12) 2939 4. 

Bacillomycins (Fig. 8) were discovered as antifungal compounds by Peypoux et al. in 1980 and Eshita et al. in 1995 from B. subtilis K In bacillomycin L congeners, the antifungal activity increases directly with increases lipophilicity, and their antifungal activity is less potent than that of clinically available polyene antibiotics amphotericin B and nystatin ... 

Gutteridge et al. [20] investigated the autoxidation of four polyene antibiotics, amphotericin B, candicidin, natamycin and nystatin. The polyenes were treated in such a way that free radical damage occurred. This was done by autoxidation of 0.1% solutions of the polyenes in dimethyl sulphoxide ... 

Amphotericin B - Observations on the immunostimulant properties of the clinically used antifungal polyene antibiotic amphotericin B (AmB) and its methylester (AME) were extended. In mice, the drugs augmented antibody formation to TNP-HSA with pronounced enhancement of secondary IgG responses,... 

Lamy-Freund MT, Ferreira VFN, Schreier S. Mechanism of inactivation of the polyene antibiotic amphotericin B. J Antibiot (Tokyo) 1985 38 753-757. 

In contrast to lipid bilayer membranes, it has been found [4] that the permeability coefficient of the human red-cell membrane to water did not change when the free cholesterol content in the membrane was varied from 0.84 to 1.87 mg/ml cells. Furthermore, the permeability of the human red-cell membrane to sulfate and some nonelectrolytes remained constant when membrane cholesterol was partially removed (for review, see [6]). These results, however, should not be taken as evidence that water transport in human red cells is independent of membrane cholesterol, since this degree of variation may be insufficient to produce alteration. In fact, extensive depletion of membrane cholesterol induces a marked increase in nonelectrolyte permeability. The effect of membrane cholesterol on the transport of water is also found in other membrane systems. For example, the polyene antibiotic. Amphotericin B, which interacts specifically with sterol-containing membranes, increases the permeability of the mucosal but not the serosal membrane of toad bladder to water and other solutes [32]. It is possible that membrane cholesterol only effects the movements through the lipid bilayer pathway. This may explain the findings that the permeabiUty coefficient of the human red cell membrane to water... 

Cholesterol and ergosterol form complexes in solution with the polyene antibiotic Amphotericin B , revealed by the development of characteristic u.v. absorption spectra and c.d. curves in the range 300—420 nm. ... 

Systemic fungal diseases (e.g. histoplasmosis and blastomycosis) are uncommon but, if untreated, often fatal. They usually take the form of lung infections or meningitis. The best treatment is still the polyene antibiotic, amphotericin B 5.14) whose mode of action is described in Section 5.4.1 (p. 192). It is usually administered intravenously. Flucytosine 4.23) is an excellent synergist (Section 4.0, p. 131), seldom given alone. Intravenous miconazole 6.23) provides alternative therapy, but there are frequent adverse reactions. An orally active analogue, ketoconazole ( Nizoral ) was introduced in 1981, and looks promising. 

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