N,N,N-Tri:methyl derivs. of amphoteric antibiotics - esp. amphotericin B or nystatin, useful as antifungals of low toxicity

摘要

Trimethyl derivs. of amphoteric antibiotics of formula (I) are new: (R is the aglycone of an amphoteric polyene antibiotic less the carboxyl gp.). Specified are N,N,N-trimethylamphotericin B (Ia) and N,N,N-trimethylnystatin. They are made by exhaustive methylation of the amino gp. in the parent antibiotic by reacting in an organic solvent with methyl halide, a methyl sulphate or sulphonate ester. (I) are antifungals, e.g. (Ia) shows fungistatic effect against various pathogenic species at 0.39-6.3 mu g/ml, and has LD50 (intravenous in mice) of 60-6-100 mg/kg i.e. 10-15 times less toxic than the parent antibiotic.