Structure-toxicity relationship of aminoglycosides: correlation of 2'-amine basicity with acute toxicity in pseudo-disaccharide scaffolds.
A new pseudo-disaccharide NB23 with a 3',4'-methylidene protection was designed and its properties were evaluated in comparison to other two structurally related pseudo-disaccharides. The basicity of the 2'-amine was found to be well correlated to acute toxicity data in mice: the increase in the basicity is associated with the toxicity increase. Based on these data, a new pseudo-trisaccharide NB45 was constructed. NB45 exhibited significant antibacterial activity while at the same time retained low acute toxicity.
Chen
Lilach
L
The Edith and Joseph Fischer Enzyme Inhibitors Laboratory, Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Hainrichson
Mariana
M
Bourdetsky
Dmitry
D
Mor
Amram
A
Yaron
Sima
S
Baasov
Timor
T
D000588:Amines / Q000737:chemistry*; D000617:Aminoglycosides / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity*; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D023382:Toxicity Tests, Acute; D014312:Trisaccharides / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity*
D000588:Amines; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004187:Disaccharides; D014312:Trisaccharides