1. Structure-toxicity relationship of aminoglycosides: correlation of 2'-amine basicity with acute toxicity in pseudo-disaccharide scaffolds.
- Author
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Chen L, Hainrichson M, Bourdetsky D, Mor A, Yaron S, and Baasov T
- Subjects
- Aminoglycosides chemical synthesis, Aminoglycosides pharmacology, Animals, Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents pharmacology, Disaccharides chemistry, Disaccharides pharmacology, Magnetic Resonance Spectroscopy, Male, Mice, Mice, Inbred ICR, Microbial Sensitivity Tests, Pseudomonas aeruginosa growth & development, Structure-Activity Relationship, Toxicity Tests, Acute, Trisaccharides chemistry, Trisaccharides pharmacology, Amines chemistry, Aminoglycosides toxicity, Anti-Bacterial Agents toxicity, Disaccharides toxicity, Pseudomonas aeruginosa drug effects, Trisaccharides toxicity
- Abstract
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.
- Published
- 2008
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