Drugs siderophore drug conjugates

Two distinct approaches can be envisioned in the development of siderophore-drug conjugates. A strategy of drug delivery utilizing the pathogen s own iron-transport system to act as a delivery system has been referred to as the Trojan Horse approach. Examples in which sulfonamides 194 , penicillins, cephalosporins and other antibiotics attached to DFO which exhibit antibacterial activity were reported. 

Siderophore drug conjugates can be utilized for both approaches. While the natural siderophores show generally low specificity, biomimetic analogs have been consistently improved to exhibit enhanced species specificity. 

Miller, M.J. Malouin. F. Microbial iron chelators as drug delivery agents The rational design and synthesis of siderophore—Drug conjugates. Acc. Chem. Res. 1993. 26. 241-249. 

The chemical nature of the linker, its size and buUciness will determine whether the drug remains attached to the siderophore or is released enzymatically into the cell. The synthesis of conjugates can proceed by derivatization of natural siderophores or by total synthesis. 

These conjugated natural antibiotics prompted the search for novel synthetic siderophores that contain a variety of drugs . 

Iron transport-mediated drug delivery synthesis and biological evaluation of cyanuric acid-based siderophore analogs and (Mactam conjugates. [M. Ghosh, M. J. Miller, J. Org. Chem. 1994, 59(5), 1020-1026] [ 46],... 

Ghosh A, Miller MJ (1993) Synthesis of novel citrate-based siderophores and siderophore- J-lactam conjugates. Iron transport-mediated drug delivery. J Oig Chem 58 7652-7659... 

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