Polymer derivatives of β-lactam antibiotics of the penicillin series

Panarin, E. F.; Solovskij, M. V.

doi:10.1016/0168-3659(89)90023-0

Cited by 9 publications

(7 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13,22−24 These rare examples show that the polymer antibiotic conjugates (PACs) reveal a higher activity, 25 efficiency against biofilms 26,27 or more stability. 24 This shows the potential of such polymer antibiotic conjugates. In most cases, the antibiotics were used as backbone modification or as end groups for hyperbranched polymers and dendrimers.…”

Section: ■ Introductionmentioning

confidence: 87%

“…One rarely followed approach is the derivatization of established antibiotics with polymers to change their activity profile and, possibly, their resistance-forming potential. − These are usually release systems. The covalent conjugation is used for biocides but less frequently for antibiotics, − e.g., penicillin. ,− These rare examples show that the polymer antibiotic conjugates (PACs) reveal a higher activity, efficiency against biofilms , or more stability . This shows the potential of such polymer antibiotic conjugates.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Poly(2-oxazoline)–Antibiotic Conjugates with Penicillins

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Section: ■ Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Poly(2-oxazoline)–Antibiotic Conjugates with Penicillins

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Most permanent PACs contain antibiotics such as doxorubicin because of their anticancer properties. , Permanent PACs which focus on the treatment of bacterial infections are rarely considered. The few known examples show that PACs can exhibit higher activity and higher efficiency against biofilms and become more stable . In previous work, we presented the conjugation of ciprofloxacin (CIP) and penicillin with poly(2-oxazoline) (POx) via end group modification.…”

Section: Introductionmentioning

confidence: 99%

“…The few known examples show that PACs can exhibit higher activity 21 and higher efficiency against biofilms 22 and become more stable. 23 In previous work, we presented the conjugation of ciprofloxacin (CIP) 24 and penicillin 25 with poly(2-oxazoline) (POx) via end group modification. In the case of penicillin, the conjugates exhibit a high resistance against the hydrolysis caused by penicillinase and are thus more active against typical penicillinresistant strains.…”

Section: ■ Introductionmentioning

confidence: 99%

Insights into the Kinetics of the Resistance Formation of Bacteria against Ciprofloxacin Poly(2-methyl-2-oxazoline) Conjugates

et al. 2018

View full text Add to dashboard Cite

The influence on the resistance formation of polymers attached to antibiotics has rarely been investigated. In this study, ciprofloxacin (CIP) was conjugated to poly(2-methyl-2-oxazoline)s with an ethylene diamine end group (Me-PMOx-EDA) via two different spacers (CIP modified with α,α'-dichloro- p-xylene-xCIP, CIP modified with chloroacetyl chloride-eCIP). The antibacterial activity of the conjugates against a number of bacterial strains shows a great dependence on the nature of the spacer. The Me-PMOx-EDA-eCIP, containing a potentially cleavable linker, does not exhibit a molecular weight dependence on antibacterial activity in contrast to Me-PMOx-EDA-xCIP. The resistance formation of both conjugates against Staphylococcus aureus and Escherichia coli was investigated. Both conjugates showed the potential to significantly delay the formation of resistant bacteria compared to the unmodified CIP. Closer inspection of a possible resistance mechanism by genome sequencing of the topoisomerase IV region of resistant S. aureus revealed that this bacterium mutates at the same position when building up resistance to CIP and to Me-PMOx-EDA-xCIP. However, the S. aureus cells that became resistant against the polymer conjugate are fully susceptible to CIP. Thus, conjugation of CIP with PMOx seems to alter the resistance mechanism.

show abstract

“…[28][29][30][31][32] To overcome the limitations associated with physical admixture and pendant attachment methods, and to better control the release characteristics of antimicrobial-eluting polymer systems, methods to chemically incorporate bioactives within the polymer backbone are being investigated. [33][34][35][36] In this study, a novel, degradable biomaterial was designed to release antimicrobials upon polymer degradation and thus locally prevent infections during the first few hours following surgery, when the implant is most susceptible to bacterial colonization. 37 The synthesis and physicochemical characterization of an ampicillin analog or prodrug, as well as chemical incorporation into a polyanhydride backbone, are described.…”

Section: Introductionmentioning

confidence: 99%

Polymeric prodrugs of ampicillin as antibacterial coatings

Prudencio

Stebbins

Johnson

et al. 2014

Journal of Bioactive and Compatible Polymers

View full text Add to dashboard Cite

A novel ampicillin prodrug containing two carboxylic acid functionalities was synthesized by reacting ampicillin with acyl chloride in the presence of base. This prodrug was subsequently converted into a poly(anhydride-amide) via solution polymerization. The polymer, which chemically incorporates the ampicillin prodrug into the polymeric backbone, was developed as a film to prevent infections associated with medical devices by controlled, localized release of antimicrobials. The robust polymer coatings exhibiting strong adhesion to stainless steel were produced under elevated temperature and reduced pressure. The in vitro hydrolytic degradation of the polymer into the ampicillin prodrug was measured and the antibacterial activity of polymer-derived coatings was examined using a Gram-positive bacterium, Staphylococcus aureus. Furthermore, the polymer cytotoxicity was screened using fibroblasts. The ampicillin prodrug demonstrated antibacterial activity and the polymer demonstrated no cytotoxic effects on fibroblasts. Based on these results, the biodegradation of the antimicrobial-based poly(anhydride-amide) into the prodrug displays substantial promise as an implant or implant coating to reduce device failure resulting from bacterial infections.

show abstract

Polymer derivatives of β-lactam antibiotics of the penicillin series

Cited by 9 publications

References 8 publications

Poly(2-oxazoline)–Antibiotic Conjugates with Penicillins

Poly(2-oxazoline)–Antibiotic Conjugates with Penicillins

Insights into the Kinetics of the Resistance Formation of Bacteria against Ciprofloxacin Poly(2-methyl-2-oxazoline) Conjugates

Polymeric prodrugs of ampicillin as antibacterial coatings

Contact Info

Product

Resources

About