Poly(2-oxazoline)-Antibiotic Conjugates with Penicillins
Autor: | Franziska Lanfer, Martin Schmidt, Christian Krumm, Elisabeth Hennes, Joerg C. Tiller, Rana Seymen, Lena Richter, Livia K. Bast |
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Rok vydání: | 2017 |
Předmět: |
Staphylococcus aureus
medicine.drug_class Carboxylic acid Antibiotics Biomedical Engineering Pharmaceutical Science Bioengineering 02 engineering and technology Oxazoline Penicillins 010402 general chemistry medicine.disease_cause 01 natural sciences Hydrolysis chemistry.chemical_compound Drug Stability medicine Escherichia coli Organic chemistry Humans Oxazoles Escherichia coli Infections Pharmacology chemistry.chemical_classification Bacteria Chemistry Organic Chemistry Bacterial Infections Penicillinase Staphylococcal Infections 021001 nanoscience & nanotechnology Antimicrobial 0104 chemical sciences Anti-Bacterial Agents Penicillin 0210 nano-technology Biotechnology medicine.drug Conjugate |
Zdroj: | Bioconjugate chemistry. 28(9) |
ISSN: | 1520-4812 |
Popis: | The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins penicillin G (PenG) and penicillin V (PenV) were attached to the end groups of different water-soluble poly(2-oxazoline)s (POx) via their carboxylic acid function. This ester group was shown to be more stable against hydrolysis than the β-lactam ring of the penicillins. The conjugates are still antimicrobially active and up to 20 times more stable against penicillinase catalyzed hydrolysis. The antibiotic activity of the conjugates against Staphylococcus aureus in the presence of penicillinase is up to 350 times higher compared with the free antibiotics. Conjugates with a second antimicrobial function, a dodecyltrimethylammonium group (DDA-X), at the starting end of the PenG and PenV POx conjugates are more antimicrobially active than the conjugates without DDA-X and show high activity in the presence of penicillinase. For example, the conjugates DDA-X-PEtOx-PenG and DDA-X-PEtOx-PenV are 200 to 350 times more active against S. aureus in the presence of penicillinase and almost as effective as the penicillinase stable cloxacollin (Clox) under these conditions. These conjugates show even greater activity compared to cloxacollin without this enzyme present. Further, both conjugates kill Escherichia coli more effectively than PenG and Clox. |
Databáze: | OpenAIRE |
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