Iron transport mediated drug delivery systems: synthesis and antibacterial activity of spermidine- and lysine-based siderophore-beta-lactam conjugates.
Conceptually, the penetration of beta-lactam antibiotics through the bacterial cell wall can be enhanced by utilizing various active transport systems such as the active iron-transport system that exists in bacteria. Several beta-lactam-siderophore analogue (microbial iron chelators) conjugates were prepared to investigate this approach. Thus, monocyclic (oxamazin) and bicyclic (carbacephalosporin) beta-lactams were separately linked to dihydroxybenzoyl derivatives of spermidine and lysine. The antibacterial activity of these conjugates has been investigated and the potential use of the iron-transport system as a drug-delivery system is discussed.
McKee
J A
JA
Department of Chemistry and Biochemistry, University of Notre Dame, Indiana 46556.
Sharma
S K
SK
Miller
M J
MJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport; D004337:Drug Carriers / Q000138:chemical synthesis*; D007501:Iron / Q000378:metabolism / Q000493:pharmacokinetics*; D007502:Iron Chelating Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008239:Lysine / Q000737:chemistry* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D017262:Siderophores; D013095:Spermidine / Q000737:chemistry* / Q000378:metabolism*; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D007502:Iron Chelating Agents; D017262:Siderophores; D047090:beta-Lactams; D007501:Iron; D008239:Lysine; D013095:Spermidine