In times of rapid spread of bacterial infections there is a growing demand for new antibiotics. Nevertheless, the number of antibiotics that reach the market is rather limited. This partially due to exploding costs for drug development and approval. A promising alternative for this expensive development is the formulation and derivatization of existing antibiotics. Especially, their combination with macromolecules is expedient, because polymeric carries afford lower toxicity, increased solubility, and prolonged activity. The antibiotic ciprofloxacin (CIP) was covalently attached to poly(2-methyloxazoline) (PMOx), poly(2-ethyloxazoline) (PEtOx) and poly (ethylene glycol) (PEG). The structures (Fig. 1a) of the different conjugates were characterized by 1H-NMR spectroscopy and ESI-MS. Moreover the minimal inhibitory concentration (MIC) of these conjugates was determined for Staphylococcus aureus (S. a), Streptococcus mutans (S. m), Escherichia coli (E.c), Pseudomonas aeruginosa (P.a), and Klebsiella pneumonia (K. p) (Fig. 1b). The results show that the conjugation strategy has a big influence of the antimicrobial activity. The direct coupling of PMOx and CIP resulted in low antimicrobial activity. Conjugates of CIP and PMOx prepared via a spacer exhibited high antimicrobial activity against Gram-positive bacteria, which is dependent on the molecular weight of the polymer, even exceeding the activity of pristine CIP. However, the conjugate shows a drastically lower activity than CIP in the case of the Gram-negative bacteria. Additionally prepared conjugates with PEtOx as well as PEG revealed a generally higher antimicrobial activity than those of the respective PMOx-CIP conjugate, but show a similar trend for the different bacterial strains. The data clearly show that the nature of the polymer backbone strongly influences the antimicrobial activity of the CIP conjugates.

Polymer antibiotic conjugates based on poly(2-oxazoline)s

253rd National Meeting (2017)

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