New N-alkyl derivatives of amphotericin B. Synthesis and biological properties.

Amphotericin B (AMB), Fig. 1 , the polyene macrolide antifungal antibiotic of high clinical importance, is the drug of choice for the treatment of deep-seated disseminated mycotic infections in humans1'2). However, the therapy is associated with toxic side effects, the most serious being the nephrotoxicity3). These undesirable effects are consequences of the poor selectivity of AMBinteraction with the animal and fungal cellular sterol targets40. To improve the biological and physico-chemical properties of the antibiotic, a program of derivative synthesis has been undertaken. It resulted in a number of AMBmodification products with increased selective toxicity and solubility in water5'6). In this report, we describe the preparation and in vitro biological properties of a novel group of 7V-alkyl AMBderivatives.