Skarbek Kornelia, Gabriel Iwona, Szweda Piotr, Wojciechowski Marek, Khan Muna A, Görke Boris, Milewski Sławomir, Milewska Maria J
Department of Organic Chemistry, Gdańsk University of Technology, Gdańsk, Poland.
Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk, Poland.
Carbohydr Res. 2017 Aug 7;448:79-87. doi: 10.1016/j.carres.2017.06.002. Epub 2017 Jun 12.
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 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.
6-磺基-6-脱氧-D-葡糖胺（GlcN6S）、6-磺基-6-脱氧-D-葡糖胺醇（ADGS）及其N-乙酰基和甲酯衍生物已被合成，并作为细菌和酵母中催化UDP-GlcNAc途径反应的酶的抑制剂进行了测试。微摩尔浓度的GlcN6S和ADGS抑制了微生物来源的葡糖胺-6-磷酸（GlcN6P）合酶。前者对真菌GlcN6P N-乙酰基转移酶也有抑制作用，但浓度为毫摩尔级。这两种化合物及其N-乙酰基衍生物均表现出体外抗菌活性，最低抑菌浓度（MIC）在0.125 - 2.0 mg/mL范围内。D-葡糖胺增强了GlcN6S的抗菌活性而非抗真菌活性，并且观察到ADGP与二肽Nva-FMDP组合具有协同抗菌作用。
