A newly identified derivative of amphotericin B: isolation, structure determination and primary evaluation of the activity and toxicity

J Antibiot (Tokyo). 2010 Sep;63(9):553-7. doi: 10.1038/ja.2010.80. Epub 2010 Jul 7.

Abstract

A new derivative of amphotericin B named amphotericin B(5) has been obtained under the following condition: amphotericin B powder was first dissolved in N,N-dimethylformamide at room temperature to obtain a solution of concentration of 2.0 mg ml(-1). Then, the solution was kept at 60 °C in an electric-heated thermostatic water bath for 48-60 h for the purpose of accelerating the degradation. Amphotericin B(5) was isolated by preparative HPLC. Its structure has been identified by means of UV, NMR and LCMS-IT-TOF as (1R, 3S, 5R, 6R, 9R, 11R, 15S, 16R, 17R, 18S, 19E, 21E, 23E, 25E, 27E, 29E, 31E, 33R, 35S, 36R, 37S)-33-[3-form-amide-3,6-dideoxy-β--mannopy-ran-osyl)oxy]-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-di-oxabicyclo [33.3.1] nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid named according to the International Union of Pure and Applied Chemistry. The activity of amphotericin B(5) was tested against Saccharomyces cerevisiae based on microbiological potency using cylinder-plate method, and the toxicities of amphotericin B and amphotericin B(5) were determined simultaneously in zebrafish embryo. The results showed that the toxicity of amphotericin B(5), as revealed by its LD(50) value, was lower than amphotericin B.

MeSH terms

  • Amphotericin B / analogs & derivatives*
  • Amphotericin B / chemistry
  • Amphotericin B / isolation & purification*
  • Amphotericin B / pharmacology
  • Animals
  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology
  • Chromatography, High Pressure Liquid
  • Lethal Dose 50
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Saccharomyces cerevisiae / drug effects
  • Spectrophotometry, Ultraviolet
  • Survival Analysis
  • Zebrafish

Substances

  • Antifungal Agents
  • Amphotericin B