Mutational biosynthesis of butirosin analogs. III. 6'-N-methylbutirosins and 3', 4'-dideoxy-6'-c-methylbutirosins, new semisynthetic aminoglycosides.
Two pairs of butirosin analogs were isolated from the fermentation broths obtained by cultivating a neamine-negative mutant of the butirosin-producing organism Bacillus circulans in the medium supplemented with 6'-N-methylneamine and gentamine C2, respectively. These amtibiotics were characterized as 6'-N-mentylbutirosins A and B (NMB-A & NMB-B), and 3', 4'-dideoxy-6'-C-methylbutirosins A and B (DCB-A & DCB-B), respectively, by chemical and spectroscopic studies. NMB-A and NMB-B exhibited broad-spectrum antibacterial activities with in vitro potency similar to or slightly less than that for butirosin A, but with greater activities against butirosin-resistant strain which contains acetylating enzyme AAC-(6')-I. The activities of NMB-A and NMB-B against Pseudomonas aeruginosa strains were relatively weak. DCB-B had broad-spectrum activity, and exhibited greatly improved activity against butirosin-resistant organisms which contain acetylating enzymes AAC(6')-I and AAC(6')-IV, and phosphorylating enzyme APH(3')-II. These new butirosin analogs were also active against some of the clinical isolates resistant to butirosins, dibekacin and/or gentamicin.
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001407:Bacillus / Q000378:metabolism*; D001419:Bacteria / Q000187:drug effects; D002076:Butirosin Sulfate / Q000096:biosynthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D008968:Molecular Conformation; D009154:Mutation
D000900:Anti-Bacterial Agents; D002076:Butirosin Sulfate