A dark green antibiotic designated as YC 73 was isolated from the culture broth of a pseudomonad. The antibiotic (C4H8N2O2S2Cu) proved to be hitherto unknown and is characterized by the presence of sulfur and copper atoms in its molecule. It is active against bacteria and fungi.
Among syntheses of DNA, RNA and protein in intact cells of E. coli B, althiomycin exhibited the strongest inhibition against protein synthesis. In the cell-free system althiomycin was confirmed to inhibit protein synthesis. On the other hand, it did not inhibit protein synthesis of reticulocyte either in the intact cells or in the cell-free system. By further studies in E. coli B systems the antibiotic was shown to inhibit the puromycin reaction, without inhibiting aminoacyl-tRNA synthesis and binding of aminoacyl-tRNA to ribosomes.
The ATP energized mitochondrial volume change phenomena employing the antibiotic and antitumor agent showdomycin has visualized the interaction with mitochondria of a respiratory inhibitor antimycin and an uncoupling agent 2, 4-dinitrophenol. These studies have been extended to other well known agents which interact with mitochondria. Dicoumarol, carbonyl cyanide p-trinuoromethoxyphenylhydrazone and heat treatment mimicked 2, 4-dinitrophenol. N-Ethylmaleimide resembled showdomycin. Valinomycin behaved like gramicidin. Our previous concept of a strategically located pivotal mitochondrial thiol group rationalized the behavior of all the above agents and hence this concept is of general significance.
The binding of blasticidin S to ribosomes is demonstrated using equilibrium dialysis. There is a single binding site per each ribosome and the association constant is 5×105 M-1. The binding site is localized in the 50S ribosomal subunit. The binding of blasticidin S to ribosomes is inhibited by gougertotin, but not affected by chloramphenicol, lincomycin, erythromycin or puromycin.
Two water-soluble basic antibiotics A-396-I and II were isolated from a culture broth of Streptoverticillium eurocidicus A-396. Both antibiotics gave similar analytical data indicative of a molecular formula C19±1H35±2013N3, but different optical activities : A-396-I, [α]D +11.6° (in water), and A-396-II, [α]D +21.8° (in water). A comparison with known antibiotics using thin-layer chromatography suggested that A-396-I is a new antibiotic and A-396-II is identical with hygromycin B.
A new antibiotic, bulgerin, was isolated from a culture broth of a streptomyces strain S-288. The strain was classified as Streptomyces aburaviensis var. tuftformis. The antibiotic is a water-soluble amphoteric substance, C17H24O10N4, λmax 230 mμ (shoulder) and 289 mμ in 0.05 N HCl, [α]D +24.0° in water, and is active against some phytopathogenic fungi.
By using cultured mammalian cells lethal effect of bleomycin was measured in terms of mean lethal dose (D37) ; the cytotoxicity on proliferative system was moderate as compared with those of other anti-tumor agents ; the dose-response revealed marked difference between two mammalian cells used. The pattern of drug response during the cell cycle was demonstrated by virtue of the synchrony method. The similarity to the pattern of X-ray response strongly suggested the involvement of the same mechanism in lethal action of bleomycin.
A new crystalline anti-tumor agent, compound 593A, has been discovered in fermentation broths of Streptomyces griseoluteus. Its presence in the fermented broth was detected by the human tumor-egg host system which was used also to help guide fermentation and isolation studies. On a weight basis, against the human adenocarcinoma (H. Ad.) # 1 in the embryonated egg, antitumor compound 593A is about 100 times as potent as hadacidin, about 4 times as potent as sodium L-tenuazonate, and about one-half as potent as mitomycin C . It also inhibits, in the egg, growth of the humansarcoma(H. S.)#1, and metastasis but not primary growth of the human epidermoid carcinoma (H. Ep.) #3. Anti-tumor compound 593A has the empirical formula C7H11ON2Cl.