Application of the synthetic aminosugars for glycodiversification: synthesis and antimicrobial studies of pyranmycin.
A divergent approach was employed for the synthesis of aminosugars, from which a novel library of aminoglycoside antibiotics (pyranmycins) was synthesized. Pyranmycins have comparable antibacterial activity as neomycin, a clinically used aminoglycoside antibiotic, against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Mycobacterium smegmatis. In addition, pyranmycins, like streptomycin, are bacteriocidal while isoniazid (INH) is bacteriostatic. Therefore, pyranmycins may provide new therapeutic options in the treatment against tuberculosis. Several members of pyranmycins also manifest modest anti-Tat and anti-Rev activities, which may aid in the development of new anti-HIV agents. Although the antibacterial activity of pyranmycins against aminoglycoside resistant bacteria is less than expected, the synthetic methodologies of utilizing a library of aminosugars can be a model for future studies of glycodiversification or glycorandomization.
Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah 84322-0300, USA.
Bryan
B
Elchert
Jie
J
Li
Jinhua
J
Wang
Yu
Y
Hui
Ravi
R
Rai
Roger
R
Ptak
Priscilla
P
Ward
Jon Y
JY
Takemoto
Mekki
M
Bensaci
Cheng-Wei Tom
CW
Chang
D000606:Amino Sugars / Q000737:chemistry*; D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D015694:Gene Products, rev / Q000096:biosynthesis / Q000235:genetics; D015696:Gene Products, tat / Q000096:biosynthesis / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014162:Transfection
D000606:Amino Sugars; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D015694:Gene Products, rev; D015696:Gene Products, tat; C475966:Pyranmycin