A new antibiotic, naphthyridinomycin, was isolated in crystalline form from the culture filtrate of Streptomyces lusitanus AY B-1026. The antibiotic is active against a large number of both gram-positive and gram-negative bacteria, and inactive against Candida albicans, Trichophyton granulosum and Microsporum gypseum. The antibiotic is toxic in mice.
New antibiotics, mannopeptins A and B, were isolated from the fermented broth of Streptomyces platensis strain FS-351. Ferrous ion is essential for the antibiotic production, since no productivity was noted with media containing less than 0.11 mM ferrous ion and maximum production was achieved at a concentration of 1.8 mM. The antibiotics are basic glycopeptides with relatively high molecular weight and are similar to ristocetin and vancomycin but can be differentiated from them in view of their chemical composition and chromatographic behavior. The antibiotics were named mannopeptin after the glycopeptide containing mannose.
Mannopeptins show in vitro antimicrobial activity against gram-positive and some gram-negative bacteria. The antimicrobial activity is unaffected by the addition of serum, and potentiated by alkaline pH or decrease in inoculum size. The antibiotics exert bectericidal effect at doses twice as high as the minimum inhibitory concentration. When the antibiotics were injected into mice through either intravenous, intraperitoneal, intramuscular or subcutaneous routes, the antimicrobial activity appeared within 15 minutes in the serum of mice and was slowly excreted in the urine. However, the antibiotics were poorly absorbed by the oral route. The antibiotics were capable of protecting mice from lethal infection produced by the intravenous injection of Staphylococcus aureus, Streptococcus pyogenes and the intraperitoneal injection of Shigella sp. and Escherichia coli, but ineffective against Salmonella typhosa.
A new antibiotic complex has been isolated from cultures of Streptomyces strain No. JA 10124. On the basis of taxonomic studies, the producing microorganism is described as Streptomyces griseoflavus (KRAINSKY, 1914) WAKSMAN et HENRICI, 1948, subsp. thuringiensis subsp. nov., type strain JA 10124. The antibiotic complex, designated as streptovirudin, was isolated from extracts of both mycelium and culture filtrate. It is a white amorphous material which consists of ten closely related components including streptovirudins A, B, C, D and E. The streptovirudin complex exhibits antibiotic activity against Gram-positive bacteria, mycobacteria, and various DNA- and RNA-viruses.
5"-Amino-3', 4', 5"-trideoxybutirosin A (IX) was synthesized through a reaction series starting from 5"-amino-5"-deoxybutirosin A (Ic), the key step being the treatment of its tetra-O-acetylpentakis-N-[(phenylmethoxy)carbonyl]-3', 4'-bis-O-(methylsulfonyl) derivative (VI) with zinc-sodium iodide. Compound IX exhibits enhanced antibacterial activities, including strains of Pseudomonas aeruginosa and Escherichia coli which are highly resistant to Ic, butirosin or gentamicin.
5"-Amino-3', 4', 5"-trideoxybutirosin A (4) was synthesized by two routes starting from the known tri-O-acetyl-tetra-N-benzyloxycarbonyl-3", 5"-O-cyclohexylidene-3', 4'-di-O-mesylbutirosin A (5). Introduction of amino function at C-5" was carried out by displacement of 5"-tosyloxy group with sodium azide either before or after 3', 4'-deoxygenation. Compound 4 shows outstanding activities against strains including Pseudomonas aeruginosa and Escherichia coli which are highly resistant to butirosin and 5"-amino-5"-deoxybutirosin A (2).
Cleavage of SV40 DNA by bleomycin was assayed quantitatively in vitro in the presence of various polynucleotides. SV40 DNA was protected from bleomycin-induced cleavage by native or denatured DNA of other origins, poly dG-C•poly dG-C, poly dA-T•poly dA-T and poly dA-T (denatured) but not by tRNA of E. coli, apurinic acid, poly dA, poly dT and various deoxyribooligonucleotides. Various bleomycins and their derivatives and various fragments of bleomycin were tested for possible activity in cleaving SV40 DNA and from the results some structure-activity relationships for the action of bleomycin to act on DNA were outlined. Actinomycin D stimulated bleomycin action while ethidium bromide inhibited it.
In vivo, at low concentrations (≤1μg/ml), the antibiotic lipiarmycin specifically inhibits RNA synthesis in Bacillus subtilis. At a much higher concentration (100μg/ml), syntheses of other macromolecules such as DNA and protein also appear to be suppressed. In vitro, the antibiotic causes 50% inhibition of DNA-dependent RNA-polymerase from B. subtilis at a concentration of 0.6μg/ml and of that from E. coliat 5-8μg/ml. The activity of Escherichia coli DNA-polymerase I is inhibited 50% at 55-65μg/ml. Lipiarmycin prevents ribonucleoside triphosphate polymerization only if added prior to the association between RNA-polymerase and DNA, and does not affect the elongation rate of RNA chains at concentrations up to 100μg/ml. At that concentration, however, the antibiotic immediately blocks the polymerization of deoxyribonucleotide triphosphates catalyzed by DNA-polymerase I.