Covalent conjugation of antimicrobial peptides (AMP) is considered an effective approach to overcome their potential degradation in vivo. As the high cost of AMP-based therapies is one of the major hurdles toward their clinical application, it is urgently needed to explore high yield reactions. Herein, the highly efficient thiol–norbornene photoclick chemistry (TNPC) was explored for AMP grafting onto chitosan. Norbornenes were introduced onto chitosan (NorChit) in an aqueous/organic system, followed by UV-triggered conjugation of N- and C-terminus cysteine-modified Dhvar5 (NorChit-Dhvar5). Up to 0.38 norbornene groups per chitosan repeating unit and up to 43% conjugation yield in NorChit-Nt-Dhvar5 (80 μmol of Dhvar5/g) were achieved, while in NorChit-Ct-Dhvar5 conjugation yield was 30% (55 μmol of Dhvar5/g). Finally, NorChit-Dhvar5 ultrathin films showed up to a 35% reduction of total adhered Gram-positive Staphylococcus epidermidis and increased the adhesion and killing of Gram-negative Pseudomonas aeruginosa compared to unmodified chitosan. Moreover, NorChit-Dhvar5 was noncytotoxic to human neonatal dermal fibroblasts, according to ISO 10993-1. Overall, our findings indicate TNPC as a high yield strategy for AMP grafting onto norbornene-functionalized biopolymers toward the fabrication of antibacterial biomaterials.
Fire blight is a major pome fruit trees disease that is caused by the quarantine phytopathogenic Erwinia amylovora, leading to major losses, namely, in pear and apple productions. Nevertheless, no effective sustainable control treatments and measures have yet been disclosed. In that regard, antimicrobial peptides (AMPs) have been proposed as an alternative biomolecule against pathogens but some of those AMPs have yet to be tested against E. amylovora. In this study, the potential of five AMPs (RW-BP100, CA-M, 3.1, D4E1, and Dhvar-5) together with BP100, were assessed to control E. amylovora. Antibiograms, minimal inhibitory, and bactericidal concentrations (minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), growth and IC50 were determined and membrane permeabilization capacity was evaluated by flow cytometry analysis and colony-forming units (CFUs) plate counting. For the tested AMPs, the higher inhibitory and bactericidal capacity was observed for RW-BP100 and CA-M (5 and 5–8 µM, respectively for both MIC and MBC), whilst for IC50 RW-BP100 presented higher efficiency (2.8 to 3.5 µM). Growth curves for the first concentrations bellow MIC showed that these AMPs delayed E. amylovora growth. Flow cytometry disclosed faster membrane permeabilization for CA-M. These results highlight the potential of RW-BP100 and CA-M AMPs as sustainable control measures against E. amylovora.
Multi‐stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine‐based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine‐sensitive and ‐resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual‐stage antiplasmodial hits.
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