In recent several years, applications of antibiotics to plant pathogenic microorganisms have been frequently reported in various scientific journals. 1)–7) But, each of these experiments was carried out under different conditions and it was difficult to compare the activities of various antibiotics to many sorts of plant pathogenic microorganisms. Therefore, authours intended to make a comparative study on the activities of various known antibiotics against main virulent plant pathogenes in our country under the same experimental condition. The purpose of this experiment is to serve as the basal data for further phytopathologic studies. But it must be noted that this experiment has been carried out only in vitro and the same results can not be always expected in vivo.
The search for antibiotics active against neoplastic cells has made much encouraging progress lately. The discovery of the effectiveness of actinomycin C against S 37 Sarcoma of mice and Walker carcinoma of rats by Hackmann1, of a new antitumor substance, sarkomycin2, 3, 4 by Umezawa, et al., azaserin5, by Stock, et al., carzinophilin6 and mitomycin7 by Hata, et al., and carcinomycin8, 9 by Hosoya and Soeda have been reported. Trichomycin9 and puromycin10, 11 were also proved to have antitumor activity. Although the results have not been so dramatic and decisive as the effect of the antibacterial antibiotics in the treatment of bacterial and rickettsial infections in the last dacade, there are bright prospect of bringing such substances into practical use.
In our laboratory, an antitumor substance was obtained from the culture fluid of a strain of streptomyces and its crude powder showed definite antitumor activity against Ehrlich ascites carcinoma in mouse12, 13, 14 and there were several evidences that the substances, named gancidin, was not identical with any of the known antibiotics which were reported to be active against malignant tumor.
The results of experiments on its production, extraction, in vitro and in vivo activities, properties, and toxicity are reported herein.
In our systematic research of Streptomyces antibiotics, a basic antimicrobial agent was obtained in a crystalline form from the culture filtrate of a Streptomyces sp., No. 7618, which was isolated from a soil sample collected near the Lake Noziri, Sinano, Japan.(1)(2) The antibiotic was named Sinanomycin. It exhibited a very wide antimicrobial spectrum, including the bacteriostatic activity on Gram positive, Gram negative, and acid fast organism and the antiviral actlvity. Especially, it exerted some protective effect against influenza A virus (PR8) infection of mice when given intraperitoneally 30 minutes before the nasal inoculation of the virus. The author studied the known antibiotics having antiviral activity and he considered that his antibiotic would be a new one(1)(2) and named it sinanomycin. However, soon later, he found that the antibiotic is similar in many properties to netropsin which was reported by Finley, et al.(3)(4) When the infrared absorption spectrum of sinanomycin sulfate was compared with that of Finley’s reports, it could not be identified as netropsin, because it exhibited no sharp peaks. Using a purified sample of netropsin hydrochloride, which had been sent from the Research Laboratory of Chas Pfizer and Co., several chemical and biological properties were examined. On the basis of the ultraviolet and the infrared absorption spectra, sinanomycin was identified as netropsin. In this paper, the results of our studies on sinanomycin are presented.
In the present time, there is no chemotherapeutic agent which is clinically useful against the diseases caused by ‘true’ viruses, although some substances suppressing experimentally virus growth have been recognized. These evidences, however, do not suggest that antiviral chemotherapy is impossible.
Streptomyces has been known to be a rich source of various kinds of interesting compounds. It produces not only antibacterial antibiotics but also anti-fungal, anti-spirochetal, anti-protozoal and anti-tumor substances. In our laboratory, the research of anti-viral antibiotics produced by streptomyces was carried out. For the screening of new antiviral antibiotics several animal viruses and bacteriophages were employed. Such employment of bacteriophages as test virus for screening of antiviral chemotherapeutic agent, however, involves an undissolved problem, whether antiphage substance has inhibitory action on animal virus, or not.
During the screening program, it was found that Streptomyces sp. E 424 and C 388 strains which related each other in morphology inhibited a bacteriophage, and that antiviral activity of the former strain was stronger than that of the latter, and from the culture filtrate of E 424 strain, the author isolated an antiviral substance in a pure form. It was recognized as a new substance and named Phagomycin.
In the present paper, the taxonomic studies of the producing strain, the cultivation and isolation procedure, and physicochemical and biological properties of the antibiotic are recorded.
In the previous papers (1)(2), the extraction processes, some properties and the antitumour activities of the crude powder of carzinocidin which was produced by the strain No. 48-B-3 were recorded. In this paper, the taxonomic studies of this strain No. 48-B-3 are presented.
The strain No. 48-B-3 was isolated from the soil at Akihabara, Tokyo and found to produce a new antitumor substance, carzinocidin, in the culture filtrate and an antifungal substance both in the mycelium and in the culture filtrate which was identified to be antimycin A. (3)(4)(5)
The authors isolated also another strain No. 21-A-2 from the soil at Kitazawa, Tokyo which produced antimycin A(6) and carzinocidin. As presented in this paper, the strain No. 48-B-3 and the strain No. 21-A-2 were found to belong to a same species.
The antitumor substance, carzinocidin was somewhat resembling to carzinomycin which was reported by Dr. Hosoya, et al.(7) in thep oint of solubility and the extraction process. Thereafter, the taxonomic studies on the strains No. 21-A-2 and No. 48-B-3 (carzinocidin-prcducing strains) and S. ganmycicus (carzinomycin-producing strain) were made, and presented in this paper. Furthermore, the comparative studies on our carzinocidin-producing strains which also produced antimycin A, the antimycin-producing strain NRRL-2288(5) and the strain No. 2A-720 which was isolated by Dr. Yonehara, et al.(8) were made, and presented in this papar. The strain NRRL-2288 was delivered to the authors by the courtesy of Dr. Hesseltine, and the strain No. 2A-720 by Dr. Yonehara, Institute of Applied Microbiology, Tokyo University.
It is one of the most important things from the clinicopathological point of view to search dihydrostreptomycin (hereafter referred to as DHSM) in the human tuberculous lesions. Baggenstoss1), Steenken2), Kitamura3), Honda4) and Canetti5) already reported on this problem. But there are few synthetic investigations designed pathologically, bacteriologically and biochemically, which are indispensable for this kind of study.
The writers are trying to investigate the problem from various standpoints. A part of them will be reported in this paper.