Amphotericin structure

Properties, structure, and derivatives of macrocyclic polyenic lactone amphotericin B 97MI12. 

Janoff AS, et al. Unusual lipid structures selectively reduce the toxicity of amphotericin B. Proc Natl Acad Sci USA 1988 85 6122. 

Amphotericin B (Fungizone), a polyene antifungal drug produced by the actinomycete Streptomyces nodosus, consists of a large ring structure with both hydrophilic... 

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. 

In spite of the overwhelming importance of the channel mechanism for the transport of alkali and alkaline earth metal ions in biological systems, only carrier transport has been studied extensively by chemists. Studies on ion channel mimics of simple structures have long been limited to antibiotic families of gramicidin, amphotericin B, and others. Several pioneers have reported successful preparation of non-peptide artificial channels. However, their claims have been based on kinetic characteristics observed for the release of metal ions through liposomal membrane and lacked the very critical proofs of channel formation. Such a situation was... 

The peptide subunit was easily incorporated into lipid bilayers of liposome, as confirmed by absorption and fluorescence spectroscopy. Formation of H-bonded transmembrane channel structure was confirmed by FT IR measurement, which suggests the formation of a tight H-bond network in phosphatidylcholine liposomes. Liposomes were first prepared to make the inside pH 6.5 and the outside pH 5.5. Then the addition of the peptide to such liposomal suspensions caused a rapid collapse of the pH gradient. The proton transport activity was comparable to that of antibiotics gramicidin A and amphotericin B. 

Carreira has reported that the aldol addition reaction to fiiran 2-carboxaldehyde may be performed on preparative scale (0.5 mol) with as little as 0.5 mol % catalyst (Scheme 8B2.12) [30], The adduct is isolated as a crystalline solid with 94% ee a single recrystallization allows access to 122 with >99% ee. Ozonolytic cleavage of the furan unmasks a carboxyl function, providing acid 124. This acid has been used in a convergent synthesis of the amphotericin C ]-C3 polyol portion. Moreover, 124 has been utilized in the synthesis of a number of pharmacologically important structures such as HMG CoA reductase inhibitors for the treatment of hypercholesterolemia [34],... 

Although not strictly within the scope of this chapter, a few other delivery systems are worth mentioning by virtue of their similarity to liposomes. Bilayer vesicle structures are not limited to phospholipids. For example, cholesterol hemisuccinate vesicles have been proposed as a deliver system for poorly soluble substances (Janoffet al., 1988). Similarly, an Amphotericin B/cholesterol... 

Fig. 12.6. Raman detection of ocular drugs in the anterior chamber. Top panel a molecular structure b Raman spectrum of aqueous solution of antibiotic drug amphotericin B (adapted from [19] c Raman spectra from aqueous humor of excised porcine eye obtained for decreasing levels of injected drug, adapted from [19] d in vivo Raman spectra of vitreous humor of rabbit eye measured through all anterior optical media before and after injection with drug, adapted from [20]...

Amphotericin B imposes its antifungal effects by binding to the sterol moiety of the membrane and damaging its structural and functional integrity (Figure 45.1). 

---