Synthesis and Evaluation of Novel 5-O-(4-C-Aminoalkyl-β-D-ribofuranosyl) Apramycin Derivatives for the Inhibition of Gram-Negative Pathogens Carrying the Aminoglycoside Phosphotransferase(3′)-Ia Resistance Determinant

Helvetica Chimica Acta 2023
Dmitrijs Lubriks, Klara Haldimann, Fatmanur Kilic, Maximilian Hartmann, Erik C Bottger, Sven N Hobbie, Edgars Sūna, David Crich

We report the synthesis and evaluation of two new apramycin 5-O-β-d-ribofuranosides, or apralogs, carrying aminoalkyl branches at the ribofuranose 4-position. This novel modification conveys excellent activity for the inhibition of protein synthesis by wild-type bacterial ribosomes and correspondingly high antibacterial activity against several Gram-negative pathogens. Notably, these new modifications overcome the reduction of antibacterial activity in other 2-deoxystreptamine-type aminoglycosides carrying a 5-O-ribofuranosyl moiety when challenged by the presence of an aminoglycoside phosphotransferase enzyme capable of acting on the ribose 5-position.

Keywords
aminoglycoside modifying enzymes | aminoglycosides | antibacterial agents | antiribosomal activity | glycosides | glycosylation
DOI
10.1002/hlca.202300138
Hyperlink
https://onlinelibrary.wiley.com/doi/10.1002/hlca.202300138

Lubriks, D., Haldimann, K., Kilic, F., Hartmann, M., Bottger, E., Hobbie, S., Sūna, E., Crich, D. Synthesis and Evaluation of Novel 5-O-(4-C-Aminoalkyl-β-D-ribofuranosyl) Apramycin Derivatives for the Inhibition of Gram-Negative Pathogens Carrying the Aminoglycoside Phosphotransferase(3′)-Ia Resistance Determinant. Helvetica Chimica Acta, 2023, Vol. 106, No. 11, Article number e202300138. ISSN 0018-019X. Available from: doi:10.1002/hlca.202300138

Publication language
English (en)