A crystalline antibiotic, active against gram-positive bacteria and mycobacteria, has been isolated from the broth of a strain of Streptomyces. This strain, which indexed H-690 in our culture collection, has been isolated from a soil sample collected from Shioya, Kobe. The chemical and physical properties show that the antibiotic is similar to thiostrepton,** isolated by Vandeputte, et al.1), the only difference consisting in the absence of leucine (or isoleucine) in its amino acid composition. Moreover, it doer not correspond with its paper chromatographic behavior to thiostrepton. The new antibiotic has been therefore designated as siomycin.
In the present paper, we intend to describe the antibiotic-producing organism and to, report the isolation and the principal characteristics of siomycin which presents some thiostrepton-like properties. The comparison is carried out with a sample of thiostrepton kindly supplied by Dr. Vandeputte.
Concerning the antibacterial test in vitro, one of the most important factors will be the solubility of compounds in water. Such substances as gramicidin J1 and chloramphenicol can be tested in a usual method owing to its strong activity though their solubility is quite slight, but the activities of the compounds low in both activity and solubility can not be determined with accuracy in usual manner. As such compounds are usually of no practical use, there is no inconvenience practically, but when one attempts the study of such basic problem as the relationship between chemical structures and antibacterial activities, the low solubility becomes a great interference. The authors met with this during the investigation of the acyl derivatives of gramicidin J1, which are highly insoluble in water. In order to solubilize these materials, we tried to use surface active agents, and in reality their utilization for this purpose has been reported in many cases1). It goes without saying that this method is only adoptable when the agents have no influence upon the activities of substances, but the reports of many researchers do not always show complete agreement, since some say it has no influence2), some claim it lowers the activities3,4) and others describe it strengthens them5,6). Then we reinvestigated this problem in hopes of finding appropriate agents applicable mainly to the gramicidin derivatives.
In the agricultural field, problems of nematodes are quite important because they cause serious damages upon many kinds of plant. The tests for nematocidal activity of various chemicals were reported1,2,3,4). But difficulties in assay method for plant parasitic nematodes gave obstacles to the large-scale screening of nematocidal substances. Recently Tarjan2) recommended that Panagrellus sp., a kind of free living nematode, is suitable as assay organism for nematocides because its size (up to about 1.4 mm long) and ease with which it can be cultured. This study was started to find systemic nematocidal antibiotics produced by actinomycetes, using free living nematodes, Rhabditis sp. and Panagrellus redivivus, as assay organisms. Moreover, nematocidal activities of some known antibiotics to these nematodes were also examined.
It has been described in the previous paper1), that 4 highly effective substances were discovered in the course of screening test for nematocidal substances produced by actinomycetes, and that some known antibiotics, such as blastmycin and antimycin A also have nematocidal activities.
In order to examine whether those nematocidal substances were also effective to plant parasitic nematodes, the tests using root-knot nematodes were undertaken in pot scale.
Although mitomycin C is known to have a remarkable antitumor effect, its practical application is often limited, because of the side toxic effects, particularly of those on the hematopoietic organ of the host1~8). The purpose of the following series of experiments is to find out which schedule of administration would give a maximum antitumor effect with a minimum side effect. Mitomycin was given in various doses, either in consecutive or in intermittent injections, and either alone or in combination with carzinophilin, and then the antitumor effects and the side effects on the host animals were compared.
In the antibiotic field, many antitumor substances have been isolated and some of them are now used in practice. A new antibiotic substance, S-339 was isolated in our laboratory from a soil streptomyces. Morphological characteristics of the strain and the properties of the substance will be published in a separate paper. The cytomorphological changes of S-339 in Yoshida sarcoma were already reported1). We are reporting here the results obtained with S-339 in the experimental treatment of Ehrlich subcutaneous solid carcinoma.
In the consecutive daily administration of antitumor antibiotics, as usually performed, the tolerated dose is usually limited by the toxic reaction of the substance on the host animal and the chronic toxic dose is not so higher than that of the acute toxic dose for this kind of antitumor substances. These observation have led us to carry out a series of experiments with the purpose of finding out administration schedules which would produce the highest possible antitumor activity with least toxic side effect. Thus, the substance S-339 was administered intravenously, using various administration schedules, to mice bearing Ehrlich solid tumor, and the results were compared.
Active filtrates or substances of microorganisms can be found rather frequently, in a screening system for antitumor antibiotics, consisting of intraperitoneal injection of culture filtrates or crude substances into tumor-bearing animals and observing changes in number and morphological characteristics of tumor cells. This intraperitoneal contact method as well as tissue culture method would be favorable for the discovery of cytotoxic substance, but substances without direct activity on tumor cells and yet causing regression in solid tumors, are liable to be left behind in this screening system. And yet, any method presently known should not be considered to be simple and satisfactory for selecting substances with either of the activities. Therefore, a method fulfilling this necessity may be desirable for the screening of antitumor substances.
The purpose of this study exists in establishment of a method which can prove either kind of the activities.
With this purpose in mind, mitomycin C 5,6,7) and 6-mercaptopurine8) were selected, as typical examples of cytotoxic substance and antimetabolic substance, respectively, and their modes of effect were compared with each other. Based on the activities commonly found for both substances, a simple method for proving either of the activities were examined.
There is only a few papers as to the question why streptomycin-dependent mutants of bacteria require streptomycin for their growth. Schaeffer1,2) stated that streptomycin-dependent mutants of E. coli require streptomycin for anaerobic glycolysis of glucose and those of B. cereus do it for cytochrome synthesis. The author isolated a streptomycin-dependent strain from a Mycobacterium “Jucho”, and observed some biochemical properties of this strain.