Aminoglycoside antibiotics. 3. Epimino derivatives of neamine, ribostamycin, and kanamycin B.
2',3'-Epimino analogues of neamine, ribostamycin, and kanamycin B possessing little or no intrinsic antimicrobial activity were designed to enhance the activity of kanamycin A against bacterial strains that elaborate aminoglycoside 3'-phosphotransferases. Routes were devised for their synthesis from the parent antibiotics and the 2'',3''-epimino analogue of kanamycin B also was prepared. None of these analogues was active against phosphotransferase-producing bacteria, although the kanamycin B derivatives showed very weak activity against nonresistant strains. At 8 and 32 microgram/mL, the 2',3'-epimino analogue of neamine produced a small synergistic effect on the activity of kanamycin A against a strain of Escherichia coli that produces aminoglycoside 3'-phosphotransferase II. The N3-(carbobenzyloxy) derivative of this analogue produced a small effect against the same strain, and it, as well as the 2'',3''-epimino analogue of kanamycin B, slightly enhanced the activity of kanamycin A against a strain of Proteus rettgeri that elaborates a similar enzyme.
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D004926:Escherichia coli / Q000187:drug effects; D007612:Kanamycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009355:Neomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D011511:Proteus / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012271:Ribostamycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D012271:Ribostamycin; D007612:Kanamycin; D010770:Phosphotransferases; D009355:Neomycin