Synthesis of azide derivative and discovery of glyoxalase pathway inhibitor against pathogenic bacteria.
A glyoxalase inhibitor was synthesized and tested against Staphylococcus aureus for first time and showed MIC90 of 20 μg/ml. Henceforth, we synthesized unnatural azide derivative of the same inhibitor to improve the biological activity. In that order, an azide carboxylate was synthesized from dimethyl tartrate by tosylation and azide substitution. The synthesized, azide compound was coupled with glutathione derivative in high yield and tested against S. aureus and showed improved MIC90 of 5 μg/ml. In general, it can be also easily converted to unnatural β-amino acid in good yield. The shown methodology will be extended to study induced suicide in Burkholderia mallei, Francisella tularensis and Mycobacterium tuberculosis in future.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States.
Benson
B
Edagwa
Yiran
Y
Wang
Prabagaran
P
Narayanasamy
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013869:Thiolester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
D000900:Anti-Bacterial Agents; D001386:Azides; D001426:Bacterial Proteins; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase
Glutathione derivative; Glyoxalase pathway; Inhibitor; Metabolism; Staphylococcus aureus