Design, synthesis, and biological evaluation of isocyanurate-based antifungal and macrolide antibiotic conjugates: iron transport-mediated drug delivery

Bioorg Med Chem. 1995 Nov;3(11):1519-25. doi: 10.1016/0968-0896(95)00134-3.

Abstract

The syntheses and preliminary biological evaluation of conjugates of a synthetic isocyanurate-based trihydroxamate siderophore with two antifungal agents, 5-FU (conjugate 9) and norneoenactin (conjugate 12), and a macrolide antibiotic, erythromycylamine (conjugate 18), are described. A 19F NMR study was used to determine the hydrolytic stability of conjugate 9 under assay conditions. Preliminary biological studies with ferric complexes of conjugates 9 and 12 indicated that these antifungal agents are recognized by Candida and perhaps are actively transported into the cell by the siderophore-transport mechanisms. While conjugate 18 did not show any significant antibacterial activity, presumably due to size restriction, the 5-FU conjugate 9 appeared to be moderately active against a variety of Gram-positive strains, and was more active than the 5-FC control against some strains of Staphylococcus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / chemical synthesis*
  • Antifungal Agents / pharmacology
  • Drug Delivery Systems
  • Drug Design
  • Iron / metabolism*
  • Macrolides

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Macrolides
  • Iron