Comparative Study for the Incorporation of a New Antifungal Family of Neoglycolipids and Amphotericin B in Monolayers Containing Phospholipids and Cholesterol or Ergosterol

Aspergillosis is a serious disease that causes the death of nearly 70% of marrow or organ transplanted patients contaminated with a filamentous fungus: Aspergillus fumigatus. To fight against this pathogenic agent, the physician only administers two commercial molecules: amphotericin B3 and itraconazole. These drugs present a certain toxicity, and resistant strains are regularly isolated. For this reason, we undertook the synthesis and the study of the antifungal properties of thenewactive neoglycolipids. These derivatives are very promising because they present the advantage of not belonging to the series currently used in human therapeutics. The developed formulas of the studied compounds are given in Figure 1. To understand better the way these neoglycolipids act and in order to improve them, we investigated their incorporation in comparison with amphotericin B in different monolayers composed of phospholipids and sterols. The main sterol of hemammaliancellmembrane is cholesterol, whereas for filamentous fungi cells, it is ergosterol, where the average molar ratio phospholipids/sterols is 70%/30%. Amphoteric in Bis known to act specifically with sterols such as cholesterol and especially ergosterol. This specificity was recently demonstrated by a study of the interaction of amphotericinBwith cholesterol or ergosterol in phospholipid monolayers and by the analysis of vesicles.10 We analyzed the incorporation of amphotericin B and different neoglycolipids into monolayers of DPPC/ergosterol. This incorporation was quantified by the measurement of the overpressure (π) in a film, as previously described. Weinvestigated the modifications also caused in the π-A isotherms of DPPC/sterol films by different concentrations of amphotericin B and glycolipid analogues, as previously described.