2623-21-4Relevant academic research and scientific papers
CEPHALOSPORIN CIPROFLOXACIN HYBRID COMPOUNDS
-
Page/Page column 34; 40; 43, (2020/06/05)
A compound of formula (Ia) and related aspects.
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 (2019/05/17)
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.
