Concentration dependent dual effect of the monolauryl ester of sucrose on the antifungal activity and absorption spectra of amphotericin B (Fungizone).
A mild detergent, the monolauryl ester of sucrose (LS), at concentrations which ranged from 0.008 to 0.03%, enhanced amphotericin B (AmB) toxicity against Saccharomyces cerevisiae and Cryptococcus neoformans cells. At higher concentrations, 0.06 to 2.5%, LS inhibited AmB effects on these two fungi. We analyzed changes in the absorption spectrum of AmB induced by LS at these two concentration ranges by comparing ratios (R values) of AmB absorbance at 409 nm, the wavelength characteristic of non-aggregated (monomeric) AmB, to absorbance at 328 nm, the wavelength characteristic of aggregated AmB. Low concentrations of LS caused a decrease in R, whereas the higher LS concentrations increased R. Therefore, LS had concentration-dependent dual effects on the antifungal activity of AmB which correlated with shifts in the physical states of AmB. The concentration range of LS required to inhibit the antifungal effects of AmB was about 1000-fold greater than the previously reported concentrations required to inhibit AmB toxicity to mammalian cells (Gruda, I., Gauthier, E., Elberg, S., Brajtburg, J. and Medoff, G. (1988) Biochem. Biophys. Res. Commun. 154, 954-958). This suggests that LS may be a useful agent to decrease AmB toxicity to host cells without affecting the antifungal effects. Moreover, increase in AmB toxicity induced by low concentrations of LS suggests the possibility that synergistic interaction between fatty acid esters and polyene antibiotics may have therapeutic value.
Brajtburg
J
J
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Gruda
I
I
Daigle
I
I
Medoff
G
G
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet; D013395:Sucrose / Q000494:pharmacology / Q000031:analogs & derivatives
D000935:Antifungal Agents; C018152:sucrose monolaurate; D013395:Sucrose; D000666:Amphotericin B