New conjugates of polyene macrolide amphotericin B with benzoxaboroles: synthesis and properties

J Antibiot (Tokyo). 2016 Jul;69(7):549-60. doi: 10.1038/ja.2016.34. Epub 2016 Mar 23.

Abstract

A novel series of conjugates of the antifungal antibiotic amphotericin B (AmB) with benzoxaboroles was synthesized. Antifungal activity of new compounds was tested on yeastβ Candida albicans and Cryptococcus humicolus and filamentous fungi Aspergillus niger and Fusarium oxysporum using the broth microdilution method. The potency of di-modified derivatives against the tested strains was similar to that of the parent AmB. New derivatives demonstrated differential toxicity against human cells (colon epithelium or red blood cells). The di-modified conjugate 2-(N,N-dimethylamino)ethylamide of 3'-N-[3-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-7-yl)propanoyl] AmB (9) showed the best combination of a high antifungal activity with a low cytotoxic and hemolytic potency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / chemistry*
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacology
  • Antifungal Agents / toxicity
  • Boron Compounds / chemical synthesis*
  • Boron Compounds / pharmacology*
  • Boron Compounds / toxicity
  • HCT116 Cells
  • Hemolysis
  • Humans

Substances

  • Antifungal Agents
  • Boron Compounds
  • Amphotericin B