Probing linker design in citric acid-ciprofloxacin conjugates

Stephen J Milner; Anna M Snelling; Kevin G Kerr; Ahmad Abd-El-Aziz; Gavin H Thomas; Roderick E Hubbard; Anne Routledge; Anne-Kathrin Duhme-Klair

doi:10.1016/j.bmc.2014.04.009

Probing linker design in citric acid-ciprofloxacin conjugates

Bioorg Med Chem. 2014 Aug 15;22(16):4499-505. doi: 10.1016/j.bmc.2014.04.009. Epub 2014 Apr 15.

Authors

Stephen J Milner¹, Anna M Snelling², Kevin G Kerr³, Ahmad Abd-El-Aziz⁴, Gavin H Thomas⁵, Roderick E Hubbard⁶, Anne Routledge⁷, Anne-Kathrin Duhme-Klair⁸

Affiliations

¹ Department of Chemistry, University of York, Heslington, York YO10 5DD, UK.
² Bradford Infection Group, University of Bradford, Bradford BD7 1DP, UK.
³ Department of Microbiology, Fewston Wing, Harrogate District Hospital, Harrogate HG2 7SX, UK; Department of Biology (Area 10), University of York, Heslington, York YO10 5DD, UK; Hull York Medical School, Heslington, York YO10 5DD, UK.
⁴ Department of Chemistry, University of York, Heslington, York YO10 5DD, UK; Department of Biology (Area 10), University of York, Heslington, York YO10 5DD, UK.
⁵ Department of Biology (Area 10), University of York, Heslington, York YO10 5DD, UK.
⁶ Department of Chemistry, University of York, Heslington, York YO10 5DD, UK; Vernalis (R&D) Ltd, Granta Park, Cambridge CB21 6GB, UK.
⁷ Department of Chemistry, University of York, Heslington, York YO10 5DD, UK. Electronic address: anne.routledge@york.ac.uk.
⁸ Department of Chemistry, University of York, Heslington, York YO10 5DD, UK. Electronic address: anne.duhme-klair@york.ac.uk.

PMID: 24794750
DOI: 10.1016/j.bmc.2014.04.009

Abstract

A series of structurally related citric acid-ciprofloxacin conjugates was synthesised to investigate the influence of the linker between citric acid and ciprofloxacin on antibacterial activities. Minimum inhibitory concentrations (MICs) were determined against a panel of reference strains and clinical isolates of bacteria associated with infection in humans and correlated with the DNA gyrase inhibitory activity. The observed trend was rationalised by computational modelling.

Keywords: Antibiotic; Citrate; Computational modelling; Siderophore.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Bacteria / drug effects
Ciprofloxacin / chemistry*
Ciprofloxacin / pharmacology*
Citric Acid / chemistry*
Citric Acid / pharmacology
DNA Gyrase / metabolism
Dose-Response Relationship, Drug
Drug Design*
Humans
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Structure-Activity Relationship
Topoisomerase II Inhibitors / chemical synthesis
Topoisomerase II Inhibitors / chemistry
Topoisomerase II Inhibitors / pharmacology*

Substances

Anti-Bacterial Agents
Topoisomerase II Inhibitors
Citric Acid
Ciprofloxacin
DNA Gyrase

Abstract

Publication types

MeSH terms

Substances

Grants and funding