Synthesis, Antibacterial and Antiribosomal Activity of the 3C-Aminoalkyl Modification in the Ribofuranosyl Ring of Apralogs (5-O-Ribofuranosyl Apramycins)

Antibiotics 2023
Dmitrijs Lubriks, Klara Haldimann, Sven N Hobbie, Andrea vasella, Edgars Sūna, David Crich

The synthesis and antiribosomal and antibacterial activity of both anomers of a novel apralog, 5-O-(5-amino-3-C-dimethylaminopropyl-D-ribofuranosyl)apramycin, are reported. Both anomers show excellent activity for the inhibition of bacterial ribosomes and that of MRSA and various wild-type Gram negative pathogens. The new compounds retain activity in the presence of the aminoglycoside phosphoryltransferase aminoglycoside modifying enzymes that act on the primary hydroxy group of typical 4,5-(2-deoxystreptamine)-type aminoglycoside and related apramycin derivatives. Unexpectedly, the two anomers have comparable activity both for the inhibition of bacterial ribosomes and of the various bacterial strains tested.

Keywords
aminoglycoside antibiotics | aminoglycoside modifying enzymes | antibacterials | antiribosomal activity | ribosomal methyltransferases
DOI
10.3390/antibiotics12010025
Hyperlink
https://www.mdpi.com/2079-6382/12/1/25

Lubriks, D., Haldimann, K., Hobbie, S., vasella, A., Sūna, E., Crich, D. Synthesis, Antibacterial and Antiribosomal Activity of the 3C-Aminoalkyl Modification in the Ribofuranosyl Ring of Apralogs (5-O-Ribofuranosyl Apramycins). Antibiotics, 2023, Vol. 12, No. 1, Article number 25. e-ISSN 2079-6382. Available from: doi:10.3390/antibiotics12010025

Publication language
English (en)