Synthesis and antimicrobial activity of 6-sulfo-6-deoxy-D-glucosamine and its derivatives

Kornelia Skarbek; Iwona Gabriel; Piotr Szweda; Marek Wojciechowski; Muna A Khan; Boris Görke; Sławomir Milewski; Maria J Milewska

doi:10.1016/j.carres.2017.06.002

Synthesis and antimicrobial activity of 6-sulfo-6-deoxy-D-glucosamine and its derivatives

Carbohydr Res. 2017 Aug 7:448:79-87. doi: 10.1016/j.carres.2017.06.002. Epub 2017 Jun 12.

Authors

Kornelia Skarbek¹, Iwona Gabriel², Piotr Szweda², Marek Wojciechowski², Muna A Khan³, Boris Görke³, Sławomir Milewski⁴, Maria J Milewska¹

Affiliations

¹ Department of Organic Chemistry, Gdańsk University of Technology, Gdańsk, Poland.
² Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk, Poland.
³ Department of Microbiology, Immunobiology and Genetics, Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Vienna, Austria.
⁴ Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk, Poland. Electronic address: [email protected].

PMID: 28628891
DOI: 10.1016/j.carres.2017.06.002

Abstract

6-Sulfo-6-deoxy-D-glucosamine (GlcN6S), 6-sulfo-6-deoxy-D-glucosaminitol (ADGS) and their N-acetyl and methyl ester derivatives have been synthesized and tested as inhibitors of enzymes catalyzing reactions of the UDP-GlcNAc pathway in bacteria and yeasts. GlcN6S and ADGS at micromolar concentrations inhibited glucosamine-6-phosphate (GlcN6P) synthase of microbial origin. The former was also inhibitory towards fungal GlcN6P N-acetyl transferase, but at millimolar concentrations. Both compounds and their N-acetyl derivatives exhibited antimicrobial in vitro activity, with MICs in the 0.125-2.0 mg mL^-1 range. Antibacterial but not antifungal activity of GlcN6S was potentiated by D-glucosamine and a synergistic antibacterial effect was observed for combination of ADGP and a dipeptide Nva-FMDP.

MeSH terms

Anti-Infective Agents / chemical synthesis*
Anti-Infective Agents / chemistry
Anti-Infective Agents / metabolism
Anti-Infective Agents / pharmacology*
Chemistry Techniques, Synthetic
Glucosamine / chemical synthesis*
Glucosamine / chemistry
Glucosamine / metabolism
Glucosamine / pharmacology*
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / antagonists & inhibitors
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / chemistry
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / metabolism
Intracellular Space / metabolism
Microbial Sensitivity Tests
Molecular Docking Simulation
Protein Conformation
Thiosugars / chemical synthesis
Thiosugars / chemistry
Thiosugars / metabolism
Thiosugars / pharmacology*

Substances

Anti-Infective Agents
Thiosugars
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
Glucosamine