Nystatin structure

The natural products Mycoticin A (22, R = H) and B (22, R = Me) belong to the skipped-polyol-polyene class of antibiotics. Our analytical interest here is to use this very complex molecular structure to demonstrate some of the tools employed, mainly for the elucidation of the polyene part of the molecule. This family of polyene macrolide class was discovered in 195045 with the finding of Nystatin (23), which is produced by the Streptomyces bacteria. The exact structure was elucidated only in 1970 by Chong and Rickards46 and, in 1971, Nystatin Ai (23) and A2 (not shown in this review) were separated. 

Nystatin (Mycostatin) is a polyene antifungal drug with a ring structure similar to that of amphotericin B and a mechanism of action identical to that of amphotericin B. Too toxic for systemic use, nystatin is limited to the topical treatment of superficial infections caused by C albicans. Infections commonly treated by this drug include oral candidiasis (thrush), mild esophageal candidiasis, and vaginitis. 

Therapeutic Function Antifungal Chemical Name Nystatin Common Name -Structural Formula ... 

Nystatin [nye STAT in] is a polyene antibiotic its structure, chemistry, mode of action, and resistance resemble those of amphotericin B. Its use is restricted to topical treatment of Candida infections because of its systemic toxicity. The drug is negligibly absorbed from the gastrointestinal tract, and it is never used par-enterally. It is administered as an oral agent ( swish and swallow ) for the treatment of oral candidiasis. Excretion in the feces is nearly quantitative. Adverse effects are rare because of its lack of absorption, but occasionally nausea and vomiting occur. 

AndreollTE. On the anatomy of amphotericin B-cholesterol pores in lipid bilayer membranes. Kidney Int 1973 4 337-45. DeKruijiff B, Demel RA. Polyene antibiotic-sterol interactions in membranes of Acholeplesma laidlawii cellsand lecithin liposomes. III. Molecular structure of the polyene antibiotic-cholesterol complexes. Biochem Biophys Acta 1974 339 57-70. HoIzRW.Theeffectsofthe polyene antibiotics nystatin and amphotericin Bon thin lipid membranes. Ann N Y Acad Sell 974 235 469-79. 

Although nystatin is a pure compound of known structure, its dosage is still expressed in terms of units. One milligram of nystatin contains not less than 2,(XX) USP units. 

Amphoteridn is a complex amphoteric polyene antibiotic that binds to cell membranes and forms a pore through which ions can pass, with consequences that include loss of potassium ions from within the cell. Since the antibiotic binds more readily to fungal cell membranes than mammalian, its action is relatively selective. It can potentiate the action of certain other antifungals. and it may be used with flucytosine. Also, it confers antifungal activity on rifampicin (normally antibacterial). As it has an appreciable renal toxicity, it needs to be used with caution in some patients. Nystatin is a polyene antibiotic similar in structure to amphotericin, often used for local treatment. 

Two other antibiotics that destroy membranes, amphotericin B and nystatin, are large ring structures that are used in treating serious systemic fungal infections. These antibiotics... 

Amphotericin B imposes its antifungal effects by binding to the sterol moiety of the membrane and damaging its structural and functional integrity (Figure 21). It is available in the form of a sterile lyophilized powder. Because it is insoluble in water, amphotericin B is marketed with sodium deoxycholate for dispersal in sterile water and 5% dextrose. The polyene antibiotics, amphotericin B, nystatin, and can-dicidin, 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. 

A model membrane system that also shows reproducible and clear 1/f behavior was described by Bezrukov and Brutyan (76). Fluctuations of current through lipid bilayers with one-sided application of three different polyene antibiotics of very close chemical structure (i.e., amphotericin B, nystatin, and mycoheptin) were studied. For one-sided application these antibiotics form channels that are weakly bound to the membrane as compared with the channels of the two-sided action. All three compounds produced pronounced noise component with spectral distribution of 1/f type (Figure 8). It was found that the noise intensity scales as the ratio of single channel conductances for amphotericin B, nystatin, and mycoheptin namely, hA hN hM = 10 5 1. For mycoheptin the spectrum is described by the function 1/f0-86 over the whole frequency range used. With two-sided application of these antibiotics, channels are more stable and strongly bound to the bilayer. In this case, significantly lower noise intensities were found the spectrum for amphotericin B was described by a single Lorentzian spectrum of relatively small amplitude (63). 

Figure 8. Membrane current noise for one-sided application of three different polyene antibiotics of a very close chemical structure shows 1 / -like spectra with intensities proportional to single-channel conductances for these antibiotics (76). Amphotericin B (l), nystatin (2), and mycoheptin (3) spectra refer to the same membrane conductance of 7.1 X 10 8 S at 10 mV.

Nystatin is a tetraene macrolide that is structurally similar to amphotericin B and has the same mechanism of action. Nystatin is not absorbed from the GI tract, skin, or vagina. 

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