Polyene Macrolide Derivatives. Iii

Bonner, Daniel P.; Mechlinski, Witold; Schaffner, Carl P.

doi:10.7164/antibiotics.25.261

Cited by 68 publications

(11 citation statements)

References 2 publications

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“…Even though the methyl ester hydrochlorides of these compounds are more soluble, they retain almost all of their antifungal activity and, more significantly, show a uniform decrease in toxicity compared to their parent compounds (284). Even though the methyl ester hydrochlorides of these compounds are more soluble, they retain almost all of their antifungal activity and, more significantly, show a uniform decrease in toxicity compared to their parent compounds (284).…”

Section: Toxicological Considerationsmentioning

confidence: 98%

Pharmaceutical Salts

Berge¹,

Bighley²,

Monkhouse

1977

Journal of Pharmaceutical Sciences

464

281

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Section: Toxicological Considerationsmentioning

confidence: 98%

Pharmaceutical Salts

Berge¹,

Bighley²,

Monkhouse

1977

Journal of Pharmaceutical Sciences

464

281

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“…In addition to their ability to inhibit the sporulation and growth of yeast and other fungi (1), some of the polyene antibiotics possess antiprotozoal activity (2) and, despite their toxicity, they have clinical applicability. For example, polyene antibiotics appear to be capable of controlling serum cholesterol levels (3,4) and prostate malfunction (5) in dogs; they also exhibit larvicidal and chemosterilant activity in some insects, apparently by blocking the uptake of dietary cholesterol (6,7).…”

mentioning

confidence: 99%

Fluorescence Studies of the Binding of the Polyene Antibiotics Filipin III, Amphotericin B, Nystatin, and Lagosin to Cholesterol

Bittman

Fischkoff

1972

Proc. Natl. Acad. Sci. U.S.A.

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The interactions of filipin III, amphotericin B, nystatin, and lagosin with sterols in aqueous suspension and in vesicles were followed by fluorescence excitation spectra and by measurement of polarized fluorescence intensities. The equilibrium constants for association of the polyene antibiotics with aqueous suspensions of cholesterol follow the order filipin IIl > amphotericin B > nystatin > lagosin, in agreement with the order reported for the extent of damage these antibiotics cause in natural and model membranes. Fluorescence polarization measurements show that hydrophobic forces are primarily responsible for the formation of the complexes. Filipin III undergoes a large enhancement in fluorescence polarization on binding to aqueous suspensions of cholesterol and epi-cholesterol, and to vesicles of lecithin-cholesterol, lecithin-fl-cholestanol, and lecithinergosterol. Small increases in polarization occur on interaction of filipin III with vesicles derived from lecithin and epi-cholesterol, thiocholesterol, and androstan-36-ol. Amphotericin B undergoes a relatively constant enhancement in fluorescence polarization on interaction with the various lecithin-sterol vesicles used and does not display the selectivity exhibited by filipin III. It is suggested that filipin IlI serves as a probe of lecithin-sterol interaction.Polyene antibiotics are potent antifungal agents produced by Streptomycetes. In addition to their ability to inhibit the sporulation and growth of yeast and other fungi (1), some of the polyene antibiotics possess antiprotozoal activity (2) and, despite their toxicity, they have clinical applicability. For example, polyene antibiotics appear to be capable of controlling serum cholesterol levels (3, 4) and prostate malfunction (5) in dogs; they also exhibit larvicidal and chemosterilant activity in some insects, apparently by blocking the uptake of dietary cholesterol (6, 7). All have a macrolide polyhydroxylic lactone ring of more than 23 atoms, with 4-7.conjugated double bonds. The discovery in 1950 of the first polyene antibiotic (8) generated considerable chemical and biological interest in this group of macrolides. The structure originally assigned to the pentaene antibiotic filipin (9-13) has been revised (14, 15) because the original work was done on a mixture of filipins (now referred to as the filipin complex) consisting of more than four components (16). The related antibiotic lagosin, which appears to be identical to, or a stereoisomer of, fungichromin, and is very similar in structure to the filipins (17), has also been subjected to extensive structural studies (11,12). Amphotericin B, a conjugated heptaene, and nystatin, whose chromophore is a conjugated tetraene distant by two methylene groups from a diene, are structurally similar. Both have a carboxyl group and an aminoglucoside group linked to the macrocyclic ring, and probably exist in the hemiketal form, at least in the crystalline state (18)(19)(20) (DMF). Experiments were done in 1 mM Tris * HCl-10 mM NaCl (pH 7.4) b...

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“…A notable success is the synthesis of AME (Mech1inski & Schaffner~ 1972;Bonner~ et a1 1972. Keim et a1~ 1973 where methylation has reduced the tOXicity and increased the apparent solubili ty of amphotericin B withou t reducing its antimycotic activity.…”

Section: Local Amphotericin Bmentioning

confidence: 99%

Parasites, Fungi, and Viruses

Geddes¹,

Williams²

1976

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Polyene Macrolide Derivatives. Iii

Cited by 68 publications

References 2 publications

Pharmaceutical Salts

Pharmaceutical Salts

Fluorescence Studies of the Binding of the Polyene Antibiotics Filipin III, Amphotericin B, Nystatin, and Lagosin to Cholesterol

Parasites, Fungi, and Viruses

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