Synthesis of ciprofloxacin dimers for evaluation of bacterial permeability in atypical chemical space

[Display omitted] We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular targ...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2015-09, Vol.25 (17), p.3468-3475
Main Authors: Ross, Audrey G., Benton, Bret M., Chin, Donovan, De Pascale, Gianfranco, Fuller, John, Leeds, Jennifer A., Reck, Folkert, Richie, Daryl L., Vo, Jason, LaMarche, Matthew J.
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Anti-Infective Agents - chemical synthesis
Anti-Infective Agents - chemistry
Anti-Infective Agents - pharmacology
Antibacterial
Antibiotic
Bacterial permeability
Chemical space
Ciprofloxacin - chemical synthesis
Ciprofloxacin - chemistry
Ciprofloxacin - pharmacology
Dimer
DNA gyrase
DNA, Bacterial - metabolism
Fluoroquinolone
Middle space
Permeability
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[Display omitted] We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular target (DNA gyrase), and translation to antibacterial activity in whole cells was demonstrated. Overall, cell permeation was governed by physicochemical properties and bacterial type. A principal component analysis demonstrated that the dimers occupy a unique and privileged region of chemical space most similar to the macrolide class of antibiotics.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2015.07.010