Imperial College London

ProfessorAlanArmstrong

Faculty of Natural SciencesDepartment of Chemistry

Professor of Organic Synthesis
 
 
 
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Contact

 

+44 (0)20 7594 5876a.armstrong

 
 
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Location

 

501EMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Evans:2019:10.1021/acs.jmedchem.8b01923,
author = {Evans, LE and Krishna, A and Ma, Y and Webb, TE and Marshall, DC and Tooke, CL and Spencer, J and Clarke, TB and Armstrong, A and Edwards, A},
doi = {10.1021/acs.jmedchem.8b01923},
journal = {Journal of Medicinal Chemistry},
title = {Exploitation of antibiotic resistance as a novel drug target: development of a β-lactamase-activated antibacterial prodrug.},
url = {http://dx.doi.org/10.1021/acs.jmedchem.8b01923},
year = {2019}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Expression of β-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to β-lactam antibiotics. In this article, we describe the development of an antibiotic pro-drug that combines ciprofloxacin with a β-lactamase-cleavable motif. The pro-drug is only bactericidal after activation by β-lactamase. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically-relevant E. coli isolates expressing diverse β-lactamases; bactericidal activity was not observed in strains without β-lactamase. These findings demonstrate that it is possible to exploit antibiotic resistance to selectively target β-lactamase-producing bacteria using our pro-drug approach, without adversely affecting bacteria that do not produce β-lactamase. This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use.
AU - Evans,LE
AU - Krishna,A
AU - Ma,Y
AU - Webb,TE
AU - Marshall,DC
AU - Tooke,CL
AU - Spencer,J
AU - Clarke,TB
AU - Armstrong,A
AU - Edwards,A
DO - 10.1021/acs.jmedchem.8b01923
PY - 2019///
SN - 0022-2623
TI - Exploitation of antibiotic resistance as a novel drug target: development of a β-lactamase-activated antibacterial prodrug.
T2 - Journal of Medicinal Chemistry
UR - http://dx.doi.org/10.1021/acs.jmedchem.8b01923
UR - http://hdl.handle.net/10044/1/69176
ER -