The isolation, characterization, and biological activities from carzinostatin were already described in a preceding paper¹⁾. When tested against Ehrlich ascites carcinoma, both culture filtrates and carzinostatin complex, the crude preparation obtained from the filtrates by adsorption and elution on acid clay, were found to exhibit marked antitumor effect. Purification of carzinostatin complex established against sarcoma 180, Bashford carcinoma 63, and ascitic form of mouse hepatoma 134, in addition to Ehrlich ascites carcinoma.

Since the publication of reports on the action of helenine¹⁾ and M-8450²⁾ against poliomyelitis in mice, this laboratory has been engaged in the sereening of streptomyces filtrates having chemoprophylactic effect against poliovirus infection in mice³⁾.

Streptomyces O-732 first called our attention since the culture filtrate of this strain showed anti-polio activity as well as antitumor activity. Extraction of the active principle(s) was attempted, and the final product obtained in a crystalline form, later designated as quinomycin complex, was shown to be highly active against gram-positive organisms, HeLa cells, Ehrlich ascites tumore^4,5), and against poliovirus infection in mice. The crystal, however, was probed to be consisting of three entities designated as A, B, and C the quinomycin A being identical with echinomycin⁶⁾ which is a cyclic polypeptide containing quinoxaline moiety.

The present paper is chiefly concerned with prophylactic effect of quinomycin complex and quinomycins A, B, and C in preventing paralysis of the mice infected with MEF₁ strain of type II poliovirus. two synthetic compounds containing quinoxaline moiety were also examined in the same manner.

The activities of streptomycin and kanamycin have been measured mainly by a biological assay method such as a cylinder plate or a disc plate method using Bacillus subtilis as the test organism. Since Wilzbach¹⁾ developed the unique method of labeling organic compound with tritium (³H) gas, tritiated biochemical material has been a new useful tool in this field.

In 1956, Andre²⁾ showed many beautiful autoradiographs of mouse organs administered with tritiated dihydrostreptomycin and tetracyline to elucidate in whice part of organs such antibiotics were distributed and retained in the body. The present authors labeled dihydrostreptomycin and kanamycin with tritium gas and investigated the fate of these antibiotics in mouse.

Two main new findings were obtained. One is that the radioactivity of tritiated dihydrostreptomycin was detected both in serum and erythricytes. The ither is that a complex of nucleoprotien and dihydrostreptomycin was obtained in vivo.

It has previously been reported¹⁾ that although kanamycin-N-methanesulfonates show less toxicity, no lowering of toxicity is exhibited in case of the compounds of NH·CHX·SO₃^- where X is replaced by alkyl or aryl group. The significant differentation has appeared to be related to the hydrolytic mechanisms of N-methanesulfonic groups. Alternative mechanisms of hydrolysis of N-methanesulfonates have thus been presented to explain the dissimilarity in toxicity beween substituted and unsubstituted N-methanesulfonates. In the present paper we wish to call further attention on the effect of substituents on the toxicity of N-methanesulfonate derivative.

Studies have been made to prepare derivatives of a type K(NH₂)₂(NH·CHCH₂X·SO₃H)₂, wherein X represents an electronegative atom or group and K represents the residual part resulted from removing of (NH₂)₁ from kanamycin molecule. It seemed likely that the system -NH·CHCH₂X>·SO₃^- would have a possibility to form a somewhat stabilized chelate ring and therefore, C-S fission would proceed in preference to N-C fission; this corresponds to the mechanism (I) in a previous paper¹⁾, lowering of toxicity being expected. It has been found that the results are in agreement with the above speculation as shown in Table 1

These derivatives except the promo derivative (III) showed significant lowering of toxicity. This is probably due to the fact that the promine atom generally fails to form hydrogen bond.

For the purpose of searching for antitumor antibiotic, we isolated Actinomycetes from the soil of Japan, and, as the result of screening the broth filtrates of Actinomycetes inhibiting Ehrlich ascites tumor, we discovered a new antibiotic, primocarcin. This paper feals with taxonimic studies of the primocarcin-producing organism, Nocardia sp. II-41 which is named Nocardia fukayae.

In the course of our antitumor antibiotic screen program using Ehrlich ascites carcinoma, a new antibiotic primocarcin was isolated in crystalline from the culture filtrate of an actinomycete designated as Nocardia fukayae¹⁾. The antibiotic is a water-soluble neutral compound having the formula C₈H₁₂N₂O₃ and shows marked tumor-inhibitory effects against ascites type of Ehrlich carzinoma and Crocker sarcoma 180. This paper deals with fermentation and isolation procefures as well as the chemical and biological properties of the antibiotic.

In the previous reports^1–5), it was found that Helminthosporium sp. fungi in which Ophiobolus miyabeanus, Helminthosporium turcicum, H. panici-miliacei, H. leersii, H. zizaniae and O. heterostrophus produced ophiobolin (m.p. 181°C, C²⁴H³²O⁴), and Pyrenophora avenae produced pyrenophorin (m.p. 174–175°C, C²⁴H³⁰O⁹.

As mentioned above, a strain of H. zizaniae was found to produce ophiobolin, was obtained as crystalline form from the culture fluid on the same strain.

The new antibiotic was isolated from culture fluid of Helminthosporium zizaniae by the author, and it wa named zizanin.

In this paper, the author wished to describe isolation, purification, chemical and physical properties and microbiological spectrum of zizanin.

In the course of screening tests, searching for new antibiotics, a strain, Streptomyces sp. No. 21544, which was isolated from a soil sample collected in Kyoto City, was found to produce a new antibiotic active against various bacteria including Gram-positive, Gram-negative and mycobacteria.

The antibiotic isolated from this strain has a broad expectrum against bacteria but weak antibiotic activity. This antibiotic was compared with known antibiotics on the basis of biological chemical and physical properties, and found to be a new antibiotic. Therefore, this antibiotic was named gougerotin.

Two crystalline antibiotics named bunlins A and B have been isolated from culture broth of Streptomyces No. 1068 obtained from the soil near Dake hot spring, Fukushima Prefecture, Japan. Bundlin A is mainly active against Sarcina lutea and similar to lankacidin¹⁾. Bundlin B is a new antibiotic of a week and narrow antimicrobial spectrum.

In the previous paper, Sakamoto^2,3) reported that two yellow crystalline antifungal antibiotics, moldcidins A and B, produced by Streptomyces No. 1069. Moldcidin A was pentaene antibiotic containing about 1.5% nitrogen. Moldcidin B was pentaene type containing no nitrogen and identical pentamycin^4,5).

Since the Streptomyces No. 1068 is unlike any of the Streptomyces described in Bergey’s Manual of Determinative Bacteriology (1957), we propose to name the organism Streptomyces griseofuscus nov. sp.

In order to discover antibiotics for agricultural chemicals, we have isolated actinomycetes from the soil, and discovered Streptomyces sp. B-28 which produces 2 antibiotics effective against Pricularia oryzae in vitro and in the greenhouse test. The one was proved to be identical with blastcidin S discovered by S. Takeuchi et al.¹⁾, and the other was named pathocidin²⁾. Pathocidin was found to be identical with 8-azaguanine as reported by Anzai, et al.³⁾, which is effective on Penicillium, Aspergillus and various phytopathogenic fungi.

In this report, the bacteriological characteristics of pathocidin-producing organism are described, and it was named Streptomyces albus var. pathocidicus.

Both streptomycin and kanamycin are toxic to auditory organ. It was reported that hearing loss developed in some patients who received daily doses of 1g of kanamycin^1,2) and also that administration of 4g kanamycin per week could be administered with a very low rate of damage of the cranial eighth nerve and with an efficacy similar to that of 2g streptomycin per week¹⁾.

In vitro studies made by the author and his associates^3–5)> have shown that kanamycin represents an additive effect with streptomycin. It has been also found that kanamycin-resistant tubercle bacilli are several times more resistant to streptomycin and streptomycin resistant tubercle bacilli are as sensitive to kanamycin as sensitive cells previously not exposed to any drug. However, this one-way partial cross-resistance does not hinder the combined use of kanamycin and streptomycin, which has resulted a more bacteriostatic effect than anyone of these drugs alone. The combined use of these two drugs, kanamycin and streptomycin, appeared to be promising for the clinical purpose, if these two drugs had not an additive damage-effect on the auditory organ (dissociation between the damaging combined effect and the bacteriostatic combined effect). Thus, the combined use of kanamycin and streptomycin, with other antituberculous drugs, has been promoted by the author and preliminary studies^6,7) have shown that kanamycin and streptomycin may be administered simultaneously without any significant side effect. It has been suggested that kanamycin may attack a different point of the auditory organ from the attack point of streptomycin. These results appeared to warrant further trial. It is the purpose of the present paper to describe some data of this trial.