Design, synthesis and antibacterial activity evaluation of ebselen derivatives in NDM-1 producing bacteria.

New Delhi-ß-lactamase-1 (NDM-1) is a type of metal-ß-lactamase. NDM-1-expressing bacteria can spread rapidly across the globe via plasmid transfer, which greatly undermines the clinical efficacy of the carbapenem. Research on NDM-1 inhibitors has attracted extensive attention. However, there are currently no clinically available NDM-1 inhibitors. Our research group has reported that 1,2-benzisoselenazol-3(2H)-one derivatives as covalent NDM-1 inhibitors can restore the efficacy of meropenem (Mem) against NDM-1 producing strains. In this study, 22 compounds were designed and synthesized, which restored the Mem susceptibility of NDM-1-expressing Escherichia coli. and its minimum inhibitory concentration (MIC) was reduced by 2-16 times. Representative compound A4 showed significant synergistic antibacterial activity against NDM-1-producing carbapenem-resistant Enterobacteriaceae (CRE) isolates. The in vitro NDM-1 enzyme inhibitory activity test showed that the IC50 was 1.26 ± 0.37 µM, which had low cytotoxicity. When combined with meropenem, it showed good combined antibacterial activity. Electrospray ionization mass spectrometry (ESI-MS) analysis demonstrates that compound A4 covalently binds to NDM-1 enzyme. In summary, compound A4 is a potent NDM-1 covalent inhibitor and provides a potential lead compound for drug development in resistant bacteria.

Effect of Antioxidant and Antimicrobial Coating based on Whey Protein Nanofibrils with TiO2 Nanotubes on the Quality and Shelf Life of Chilled Meat.

Whey protein nanofibrils (WPNFs) can be used in edible films and coatings (EFCs) because of its favorable functional properties, which rely on its well-ordered ß-sheet structures, high hydrophobicity, homogeneous structure, and antioxidant activity. In the present study, WPNF-based edible coatings with glycerol (Gly) as plastic and titanium dioxide nanotubes (TNTs) as antimicrobial agents were studied. TNTs not only showed greater antibacterial activity than titanium dioxide nanoparticles (TNPs), but also increased interactions with WPNFs. The WPNF/TNT film had a smooth and continuous surface and was homogeneous with good mechanical properties. WPNF/TNT edible coatings (ECs) can help improve lipid peroxidation and antioxidant activity, limit microbial growth, reduce weight loss, and extend the shelf life of chilled beef. Given that the WPNF/TNT film components are low cost and show high antioxidant and antimicrobial activity, these optimized films have potential applications for various food products, including raw and chilled meat.