title: Siderophore-fluoroquinolone conjugates containing potential reduction-triggered linkers for drug release: synthesis and antibacterial activity.
abstract: Syntheses of two Siderophore-fluoroquinolone conjugates with a potential reduction triggered linker for drug release are described. The "trimethyl lock" based linker incorporated in the conjugates was designed to be activated by taking advantage of the reductive pathway of bacterial iron metabolism. Electrochemical and LC-MS studies indicated that the linker is thermodynamically reducible by common biological reductants and the expected lactonization proceeds rapidly with concomitant release of the drug. Antibacterial activity assays revealed that conjugates with the reduction-triggered linker were more potent than their counterparts with a stable linker, which suggests that drug release occurs inside bacterial cells.
authors: Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN, 46556, USA.
authors: Cheng
authors: C
authors: Ji
authors: Marvin J
authors: MJ
authors: Miller
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D024841:Fluoroquinolones / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D017262:Siderophores / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D017262:Siderophores; D007501:Iron