Design, synthesis, and biological evaluation of isocyanurate-based antifungal and macrolide antibiotic conjugates: iron transport-mediated drug delivery.
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.
Ghosh
M
M
Department of Chemistry and Biochemistry, University of Notre Dame, IN 46556, USA.
Miller
M J
MJ
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D016503:Drug Delivery Systems; D015195:Drug Design; D007501:Iron / Q000378:metabolism*; D018942:Macrolides
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D018942:Macrolides; D007501:Iron