Low toxic derivatives of istamycin B: synthesis and preliminary evaluation.
3-O-Demethylistamycin B derived from istamycin B was one of the most potent aminoglycoside antibiotics against various bacteria. 3-O-Demethylistamycin B, however, showed considerable acute toxicity in mice. The authors attempted to prepare the derivatives of istamycin B having high potency and low toxicity. The selective N-acylation or N-amidination at the C-2 position of istamycin B could not improve the acute toxicity. The replacement of the amino group at the C-2 position of istamycin B by a hydroxyl group markedly decreased the acute toxicity. Among 2'-deamino-2'-hydroxyistamycins, 4-N-(beta-alanyl)-2'-deamino-3-O-demethyl-2'-hydroxyistamycin B0 (9d) showed good antibacterial activity against Gram-positive and Gram-negative bacteria and a low acute toxicity in mice.
Ikeda
D
D
Institute of Microbial Chemistry, Tokyo, Japan.
Gomi
S
S
Hamada
M
M
Kondo
S
S
Takeuchi
T
T
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C022949:istamycins