A search for antitumor agents, derived from streptomycetes, is now in progress in the world. As a result of this effort, not a few substances were discovered and described. The following tumor inhibitory agents have been extracted so far in our laboratory: luteomycin1), carzinophilin2) and mitomycin3).
A substance, described in this paper, was extracted from culture filtrate of a streptomyces isolated newly from a soil. Its inhibitory activity was limited only to the tumor growth, in contrast to the other three substances, which have also antibacterial properties. Using this substance, a mild but definite effect was obtained not only on Ehrlich ascitic tumor but on its subcutaneous tumor. As the cultural characteristics of the streptomyces were not in accordance with any described species of streptomyces, it was given the name of Streptomyces melanogenes.
Some physicochemical properties of active substance indicated it might be a melanin-like substance. For this reason the name of melanomycin was given to this active principle. Melanomycin was obtained as a blackish amorphous powder, not crystallized yet. It is the purpose of this paper to describe production, fermentation, assay method, purification, and physicochemical properties of melanomycin. The description of the melanomycin-producing strain and the experiments on the tumor-inhibitory activity will be the subject of later studies.
In the first report1) the effect of pluramycin crude powder on Ehrlich carcinoma of mice was described, and in the second report2) process of isolation and properties of pluramycin A were described. Pluramycin was produced by a streptomyces assigned to S. pluricolorescens, n. sp., and it was extracted from the cultured broth with ethyl acetate at pH 7.0, and after the evaporation of the solvent it was purified by the countercurrent distribution between ethyl acetate and phosphate buffer of pH 5.3. Then, existences of pluramycins A and B were found. Pluramycin A had basic characters, and its free base was obtained as orange needle or plate crystals2). The free base was soluble in methanol, ethanol, acetone, chloroform, ethyl acetate, butyl acetate, benzene and ethyl cellosolve. It was slightly soluble in ether and hexane, and insoluble in petroleum ether and water. It was soluble in acid water and rapidly decreased the activity. It was differentiated from known antibiotics by analytical results and the infrared spectra. The acid hydrolysis did not give ninhydrin positive spots.
Acute and chronic toxicities and effect of pluramycin A on Ehrlich carcinoma were studied and the results are presented in this paper.
In the treatment of chronic sinusitis chemotherapeutic agents are widely used. However, in children, some kinds of therapeutic measure can be applicable only with difficulty. Furthermore, the problem of the strains which are resistant against penicillin and streptomycin and that of severe side effects of these chemicals frequently impede the application of chemotherapy.
The present author examined the therapeutic effect of broad spectrum antibiotics other than penicillin and streptomycin against chronic sinusitis in children. Only oral administration was used and no other local treatment was applied.
Though such general administration of antibiotics in the treatment of the disease in adults has been already reported by Ohsawa1), Peterson and Hadley2)and Arslan and De Vido3), Menger4), Lumin5) and others, no report has been made on its application to children.
Accompanying wide use of chemotherapeutic agents, the drawbacks gradually increased. Especially the problem of resistant strains has been attracting attention since the works by Rammelkamp1), Spink2) and others on the resistance to penicillin. In Japan, staphylococcus is one of the pathogens which are found resistant most frequently.
The author attempted to examine the sensitivity of the staphylococci which were found in the maxillary sinus of children to various antibiotics. These staphylococci were supposed to be important in the chemotherapy of chronic sinusitis in children. The studies were made from October 1955 to May 1956.