The number of new antibiotics that reach the market is currently much lower than that of newly developing antibiotic-resistant bacterial strains. This causes serious health problems even in industrialized societies. Thus, the need for antibiotics with changed activity profiles and resistance forming potential is great. A common way to achieve this is derivatization of established antibiotics. We have investigated the antimicrobial behavior of polymer antibiotic conjugates, which has been rarely investigated. Poly(2-oxazoline)s (POx) are biocompatible polymers considered as alternative to Poly(ethylene glycol) (PEG) and therefore promising candidates for the conjugation with antibiotics. Covalent conjugates of POx with the antibiotic ciprofloxacin (CIP) were found to be antimicrobially active against several nosocomial bacterial strains. Thereby, the activity is controlled by the nature of the linker between CIP and the polymer, the nature of the polymer itself, and the length of the polymer chain. In the some cases, the molar antibacterial activity of the conjugates even exceeds that of pristine CIP. It was further shown that the resistance formation of S. aureus and E. coli against the conjugates is significantly delayed compared the CIP Conjugates of POx with penicillin G and penicillin V, respectively, were also found to be active. Here, the length of the polymer does not play a significant role, due to the fact that these antibiotics are not required to cross the cell membrane to be active. Further, the penicillin POx conjugates were found to be less susceptible to hydrolysis by the enzyme penicillinase, which makes them active against penicillinase-producing and thus resistant bacterial strains.

Poly(2-oxazoline) conjugates with antibiotics

2019 Spring National Meeting

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