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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.

SUBMITTER: Ji C

PROVIDER: S-EPMC5808879 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Siderophore-fluoroquinolone conjugates containing potential reduction-triggered linkers for drug release: synthesis and antibacterial activity.

Ji Cheng C Miller Marvin J MJ

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 20150208 3

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 ...[more]

PMID: 25663417

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