Antibacterial Conjugates of Kanamycin A with Vancomycin and Eremomycin: Biological Activity and a New MS-Fragmentation Pattern of Cbz-Protected Amines.
Pavel N SolyevElena B IsakovaEvgenia N OlsufyevaPublished in: Antibiotics (Basel, Switzerland) (2023)
A significant increase of microbial resistance to glycopeptides (especially vancomycin-resistant enterococci and Staphylococcus aureus ) prompted researchers to design new semisynthetic glycopeptide derivatives, such as dual-action antibiotics that contain a glycopeptide molecule and an antibacterial agent of a different class. We synthesized novel dimeric conjugates of kanamycin A with glycopeptide antibiotics, vancomycin and eremomycin. Using tandem mass spectrometry fragmentation, UV, IR, and NMR spectral data, it was unequivocally proven that the glycopeptide is attached to the kanamycin A molecule at the position 1 of 2-deoxy-D-streptamine. New MS fragmentation patterns for N -Cbz-protected aminoglycosides were discovered. It was found that the resulting conjugates are active against Gram-positive bacteria, and some are active against vancomycin-resistant strains. Conjugates of two different classes can serve as dual-target antimicrobial candidates for further investigation and improvement.
Keyphrases
- methicillin resistant staphylococcus aureus
- staphylococcus aureus
- tandem mass spectrometry
- mass spectrometry
- cancer therapy
- high performance liquid chromatography
- ultra high performance liquid chromatography
- liquid chromatography
- ms ms
- high resolution
- multiple sclerosis
- biofilm formation
- simultaneous determination
- gas chromatography
- magnetic resonance
- microbial community
- drug delivery
- escherichia coli
- electronic health record
- solid phase extraction
- magnetic resonance imaging
- big data
- high resolution mass spectrometry
- machine learning
- pseudomonas aeruginosa
- multidrug resistant
- wound healing
- aqueous solution