Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents.
Glyco-optimization (OPopS) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives. Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs). Among them, compounds 8b,g,i,l, and 8u with 2"-amino, 2",3"-diamino, 2",4"-diamino, 3",4"-diamino, 3"-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(-) bacteria. Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1-2 microg/mL range.
Yao
Sulan
S
Department of Chemistry, Optimer Pharmaceuticals, Inc., 10110 Sorrento Valley Road, Suite C, San Diego, CA 92121, USA. ssucheck@optimerpharma.com
Sgarbi
Paulo W M
PW
Marby
Kenneth A
KA
Rabuka
David
D
O'Hare
Sean M
SM
Cheng
Mayling L
ML
Bairi
Mrunali
M
Hu
Changyong
C
Hwang
San-Bao
SB
Hwang
Chan-Kou
CK
Ichikawa
Yoshi
Y
Sears
Pamela
P
Sucheck
Steven J
SJ
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014312:Trisaccharides / Q000138:chemical synthesis / Q000494:pharmacology
D000617:Aminoglycosides; D000890:Anti-Infective Agents; D014312:Trisaccharides