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

Dmitrijs Lubriks; Klara Haldimann; Sven N Hobbie; Andrea Vasella; Edgars Suna; David Crich

doi:10.3390/antibiotics12010025

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

Antibiotics (Basel). 2022 Dec 24;12(1):25. doi: 10.3390/antibiotics12010025.

Authors

Dmitrijs Lubriks¹, Klara Haldimann², Sven N Hobbie², Andrea Vasella³, Edgars Suna¹, David Crich^{4

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Affiliations

¹ Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, Latvia.
² Institute of Medical Microbiology, University of Zurich, Gloriastrasse 30, 8006 Zürich, Switzerland.
³ Organic Chemistry Laboratory, ETH Zürich, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland.
⁴ Department of Pharmaceutical and Biomedical Sciences, University of Georgia, 250 West Green Street, Athens, GA 30602, USA.
⁵ Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
⁶ Department of Chemistry, University of Georgia, 302 East Campus Road, Athens, GA 30602, USA.

Abstract

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.

Grants and funding

This work was supported in part by ERDF (Post-Doc Latvia, project No.1.1.1.2/VIAA/3/19/586).