28031-33-6Relevant academic research and scientific papers
Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug
Evans, Lindsay E.,Krishna, Aishwarya,Ma, Yajing,Webb, Thomas E.,Marshall, Dominic C.,Tooke, Catherine L.,Spencer, James,Clarke, Thomas B.,Armstrong, Alan,Edwards, Andrew M.
, p. 4411 - 4425 (2019)
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 prodrug that combines ciprofloxacin with a β-lactamase-cleavable motif. The prodrug 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 prodrug 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.
CEPHALOSPORIN CIPROFLOXACIN HYBRID COMPOUNDS
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Page/Page column 34; 39; 40, (2020/06/05)
A compound of formula (Ia) and related aspects.
CEPHALOSPORIN DERIVATIVES USEFUL AS β-LACTAMASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF
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Page/Page column 55, (2011/09/21)
The present invention relates to cephalosporin derivatives having β- lactamase inhibitory activity. The compounds are useful in preventing or treating bacterial resistance to an antibiotic, e.g. a β-lactam antibiotic. Disclosed herein are compounds that are inhibitors of class B metallo-β-lactamases, as well as class A, C, and D serine β-lactamases. In some preferred embodiments, the compounds are 3'- thiobenzoate derivatives of a cephalosporin. Pharmaceutical compositions, methods, uses, kits and commercial packages comprising the compounds are also disclosed.
