Chemical ionization mass spectrometry, using isobutane as a reactant gas, is shown to be useful in the structural characterization of representative 16-membered ring macrolide antibiotics. The spectra of spiramycin I, spiramycin III, and niddamycin contain relatively intense protonated molecule ion peaks (MH+) making establishment of molecular formulae straightforward. There are relatively few fragment ion peaks in comparison with the corresponding electron impact mass spectra, but these peaks are nonetheless highly significant. The major fragmentations observed involve sequential loss of the sugar moieties and loss of other small molecules such as water, acetic acid, and methanol. Scission of carbon-carbon bonds is uncommon. The nature of these reactions and the mechanisms responsible are discussed briefly.
The mode of action of cryomycin upon Staphylococcus aureus IFO 3061 and Bacillus subtilis IFO 3037 has been investigated. Cryomycin inhibited the syntheses of protein, RNA and DNA to almost the same degree. It caused a rapid increase of endogenous and exogenous respiration in the test organisms at minimum growth inhibitory concentrations. It was concluded that the primary effect of cryomycin was on the coupling of oxidative phosphorylation followed by secondary effects such as membrane damage, and protein and nucleic acid syntheses. Cryomycin also caused the leakage of A260mμ, absorbing materials from most of the Bacillus species.
Antibiotic P-42-1 was isolated from the culture filtrate of Actinomyces tumemacerans strain INMI.P-42, and its detailed physicochemical and biological properties were investigated. The antibiotic was obtained as yellow crystals and its molecular formula was estimated to be G27H24N2O9. It was found to be highly active on a wide variety of gram-positive bacteria and fungi, whereas much less active on gram-negative bacteria. The antibiotic was cytotoxic to HeLa cell cultures and exhibited antitumor activity on EHRLICH ascites tumor in mice. Antibiotic P-42-1 was found to be closely related to antibiotic BA180265 A (kanchanomycin) and albofungin. According to structural studies on albofungin recently conducted by Russian workers, antibiotic P-42-1 proved to be identical with albofungin and kanchanomycin.
A new complex of phleomycin-bleomycin group antibiotics, YA-56, was isolated from the culture broth of a streptomycete designated as strain MCRL 0387 and identified as a new variety of Streptomyces humidus NAKAZAWA and SHIBATA in IMAMURA et al., 1956. Ultra-violet irradiation of strain MCRL 0387 gave a high-yielding mutant which formed blue aerial mycelium instead of the grayish aerial mycelium of the original strain. Fermentative production of the antibiotics YA-56 complex is described.
Isolation, purification and physicochemical properties of the antibiotic complex YA-56, a family of phleomycin-bleomycin group, are described. The antibiotic YA-56 complex was found to be composed mainly of two active components named YA-56 X and Y. These components were clearly differentiated from the reported phleomycins and bleomycins by their physicochemical properties. However, by direct comparison, YA-56 X was found to be identical with zorbamycin reported recently. YA-56 Y was recognized to be a new antibiotic.
With many clinical isolates of Staphylococcus aureus and Escherichia coli, we have found with our statistical analysis that there is a correlation between the increase in the minimum inhibitory concentration (MIC) and the number of antibiotics to which strains are resistant. However, detailed examination of the results shows that not only does the MIC increase with acquired multiple drug resistance but the type can be differentiated into three types, both with S. aureus and E. coli.
BB-K 8, a new semisynthetic aminoglycosidic antibiotic, was evaluated for ototoxicity, nephrotoxicity and neuromuscular blocking activity in the cat. As a reference, kanamycin was tested by the same experimental methods. Employing equivalent doses in terms of the free base and 7 days of intraperitoneal treatment, BB-K 8 and kanamycin were found to be similarly ototoxic and nephrotoxic. Acutely, both compounds also demonstrated a similar neuromuscular blocking activity after large intravenous doses.
Siomycin is a sulfur-containing peptide antibiotic which resembles thiostrepton in structure2) and is produced by Streptomyces sioyaensis1). The antibiotic shows high activity against various gram-positive bacteria including Mycobacterium tuberculosis and many clinical resistant strains of Staphylococcus. YAGI et al.3) recently reported that the yield of siomycin is increased three- to four-fold by the addition of elemental sulfur to the fermentation broth where the sulfur is oxidized to thiosulfate, and also that the incorporation of thiosulfate ions is one of the key steps in siomycin biosynthesis. This work has been carried out in order to prepare S35-siomycin for pharmacological use, and owes much to the above work of YAGI et al.3)