Abstract
Infections caused by bacteria resistant to antibiotics are an increasing problem. Multivalent antibiotics could be a solution. In the present study, a covalent conjugate between Ciprofloxacin and a G0-PAMAM dendrimer has been synthesized and tested against clinically relevant Gram-positive and Gram-negative bacteria. The conjugate has antimicrobial activity and there is a positive dendritic effect compared to Ciprofloxacin itself.
Highlights
Antimicrobial resistance to antibiotics is an increasing problem worldwide
Apart from the effect on the central nervous system, a serious issue is that the known efflux-pump inhibitors lack specificity for bacterial efflux pumps, but are inhibitors for pumps found in humans, like glycoprotein P, and can interfere with the hERG-channel in the heart lengthening the QT-interval, increasing the risk of cardiac arrest [15,16]
The control dendrimer (5) lacked antimicrobial activity whereas the dendrimer Ciprofloxacin conjugate (4) showed highest activity in terms of MIC values expressed in μM showing a clear positive dendritic effect, which becomes even bigger if the MIC values are calculated relative to the number of Ciprofloxacines
Summary
Antimicrobial resistance to antibiotics is an increasing problem worldwide. the World. A possible solution to efflux-mediated resistance could be modifications of known antibiotics so they are not substrates for efflux-pumps while keeping the antimicrobial activity. D’Emanuele and coworkers [17] discovered that the beta-blocker propranolol covalently conjugated to a PAMAM-dendrimer was internalized by human cells. This was interesting, because propranolol itself is known to be a substrate for the glycoprotein P pump. Molecules 2020, 25, 1389 conjugated to a PAMAM-dendrimer was internalized by human cells.
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