Synthesis and antibacterial activity of desosamine-modified macrolide derivatives.
Structural factors behind erm macrolide resistance were studied through synthesis of new macrolide derivates possessing truncated desosamine sugar moieties and subsequent determination of their antibacterial activity. Synthesized compounds with 2'-deoxy and 3'-desmethyl desosamine rings demonstrated decreased antibacterial activity on the native Staphylococcus aureus strain and were inactive against constitutively resistance S. aureus. The obtained results indicate that steric repulsion between the dimethylated A2058 and desosamine ring cannot be considered as a primary reason for erm-resistance.
Department of Chemistry & Biomolecular Science, Clarkson University, 8 Clarkson Ave., Potsdam, NY 13699-5810, United States.
Nicolas
N
LeTourneau
Pavan
P
Vimal
Dorota
D
Klepacki
Alexander
A
Mankin
Artem
A
Melman
D000606:Amino Sugars / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000606:Amino Sugars; D000900:Anti-Bacterial Agents; D018942:Macrolides; C110125:desosamine