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Effects of the detergent sucrose monolaurate on binding of amphotericin B to sterols and its toxicity for cells.

Abstract：

:Amphotericin B (AmB) is a potent antifungal agent used to treat patients with systemic mycoses. The cytotoxicity of AmB is related to its binding to membrane sterols and its clinical usefulness is based on its greater affinity to ergosterol, the fungal sterol, compared to the mammalian cell sterol, cholesterol (1-3). Here we report that sucrose monolaurate (L.S.) decreased the binding of AmB to cholesterol without interfering with its binding to ergosterol. Furthermore, the toxicity of AmB for mouse erythrocytes (RBC) and cultured mouse fibroblasts, L-929, cells was significantly decreased by low concentrations of L.S., whereas under the same conditions, its toxicity for Candida albicans was unaffected. We observed a very good correlation between the spectroscopic and cell studies. The results reported here on the effects of L.S. on the selectivity of AmB toxicity for fungal cells compared to animal cells and the relative nontoxic nature of sugar esters suggest a potential for compounds of this type to enhance the therapeutic index of AmB.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Gruda I,Gauthier E,Elberg S,Brajtburg J,Medoff G

doi

10.1016/0006-291x(88)90232-x

subject

Has Abstract

pub_date

1988-08-15 00:00:00

pages

954-8

issue

3

eissn

0006-291X

issn

1090-2104

pii

0006-291X(88)90232-X

journal_volume

154

pub_type

杂志文章

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