Ficellomycin is a new basic antibiotic produced by Streptomyces ficellus. Ficellomycin, C₁₃H₂₄N₆O₃, inhibits the growth of gram-positive bacteria in vitro and is effective in the treatment of experimental Staphylococcus aureus infections in mice.

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Feldamycin, a new antibacterial agent, and nojirimycin, a previously described antibiotic, have been isolated from cultures of Streptomyces ficellus. Feldamycin, C₁₇H₂₅N₇O₅, is an amphoteric compound which inhibits a variety of bacteria in vitro but is found to be ineffective in the treatment of experimental bacterial infections in mice. Nojirimycin (5-amino-5-deoxy-D-glucose) has been isolated previously from cultures of several species of streptomycetes.

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A new antibiotic XK-90 is produced by Streptomyces sp. MK-90 and is active against Gram-positive and Gram-negative bacteria. The taxonomy of the organism, fermentation, isolation and physicochemical and biological properties are described.

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A new antibiotic, aplasmomycin, which inhibits growth of Gram-positive bacteria including mycobacteria in vitro, and plasmodia in vivo was obtained from a strain of Streptomyces griseus isolated from shallow sea sediment in Sagami Bay. The antibiotic forms colorless
needle-like crystals and has a molecular formula of C₄₁H₆₀O₁₄Na. Based on its physical and chemical properties, aplasmomycin was concluded to be a new antibiotic. The antibiotic was produced in selected media devised to relate to a marine environment.

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The antitumor protein actinoxanthin exhibits high inhibitory activity against a number of gram-positive bacteria and some strains of transplantable leucoses and related tumors. Actinoxanthin was shown to consist of a single polypeptide chain crosslinked by two disulfide bonds and to contain 107 amino acid residues. Reduced and alkylated actinoxanthin was digested with chymotrypsin, thermolysin and trypsin. Based on the sequence analysis of fragments so obtained the complete amino acid sequence and the location of disulfide bonds of actinoxanthin has been proposed. The high degree homology of some regions of actinoxanthin and the antitumor protein neocarzinostatin have been revealed.

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Carbon magnetic resonance establishes conclusively that six polyene macrolide antibiotics containing keto groups (the heptaene amphotericin B, the tetraene-diene nystatin A₁, and the tetraenes tetrin A, tetrin B, pimaricin, and lucensomycin) exist in the hemiketal form in solution. Their spectra all contain a hemiketal carbon's absorption near 97 ppm but lack a keto carbon's absorption near 210 ppm. The non-polyenic macrolide erythromycin, on the other hand, exists in the keto form.

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Iturin A, an antifungal lipopeptide characterized by the presence of homologous liposoluble β-aminoacids was found to be the active component to bacillomycin B, bacillomycin R and eumycin. Iturin A was identified by thin-layer chromatography, aminoacid analysis and by characterization of liposoluble aminoacids and peptides. Another two preparations: the antibiotic of RAUBITSCHEK and the bacillomycin of LANDY et al. contain components of the same structural type but they are different from iturin A.

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Bikaverin obtained by supplementing cultures of Fusarium oxysporum with singly and doubly ¹³C labeled acetate was enriched by approximately 0.5 atom percent with the ¹³C isotope. At this low enrichment ¹³C NMR spectra of samples labeled from (1-¹³C)- and (2-¹³C) acetate did not show, unequivocally, the pattern of isotopic incorporation. Small sample size, poor solubility and difficulties in the assignment of resonances also restricted the amount of information that could be obtained from the ¹³C NMR spectrum of the sample labeled from (1, 2-¹³C) acetate. The difficulty was overcome by using ¹³C homonuclear single-frequency decoupling in conjunction with ¹H heteronuclear decoupling to locate bonded ¹³C-¹³C pairs. The carbon skeleton of bikaverin was shown to be biosynthesized entirely by condensation of acetate units and the pattern of assembly was established.

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Ceftezole, a new cephalosporin antibiotic similar to cefazolin, has the following chemical structure: (6R, 7R)-8-oxo-7-[2-(1H-tetrazol-1-yl)acetamido]-3-[ (1, 3, 4-thiadiazol-2-ylthio)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-carboxylic acid. Ceftezole was found to be a broad-spectrum antibiotic, active in vitro against many species of gram-positive and gram-negative bacteria except Pseudomonas aeruginosa, Serratia marcescens and Proteus vulgaris. The activity of ceftezole against clinical isolates of Escherichia coli and Klebsiella spp. appeared to be nearly equal to that of cefazolin and higher than those of cephaloridine and cephalothin. Cross-resistance was observed between ampicillin and cephaloridine, but not between ampicillin and ceftezole, in susceptibility tests on clinical isolates of P. mirabilis. The in vitro activity was little affected by the inoculum size, the presence of human serum or the test medium.
Ceftezole exhibited apparent bactericidal activity at the concentrations above the minimum inhibitory concentration (MIC) against both S. aureus and E. coli. The development in vitro of resistance by S. aureus 209P and E. coli NIHJ to ceftezole after 16 transfers was similar to or somewhat slower than that to other drugs tested. Ceftezole was relatively stable in nutrient broth and minimally degraded in the serum or tissue homogenates of rats.
Ceftezole, in a single subcutaneous administration, exhibited somewhat less efficacy in mice against intraperitoneal infections with Streptococcus pyogenes, S. pneumoniae, E. coli, K. pneumoniae or P. mirabilis than either cephaloridine or cefazolin. However, ceftezole exhibited efficacy similar to that of cephaloridine or cefazolin when administered in three doses. Furthermore, ceftezole was as effective as cefazolin in the treatment of experimental abscesses in (nice caused by subcutaneous inoculation with S. aureus.

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The distribution of ceftezole in blood and tissues and its excretion after intramuscular or intravenous administration of single doses of 10 and 20 mg/kg were compared with those of cefazolin, cephaloridine and cephalothin. Blood levels of ceftezole in rats and rabbits were lower than those of cefazolin, and higher than those of cephaloridine and cephalothin. Retention time of ceftezole in the blood was somewhat shorter than that of cefazolin. However,
blood levels of ceftezole in dogs were nearly the same as those of cefazolin and cephaloridine. The rate of urinary excretion of ceftezole in 24-hour urine after administration in rats and rabbits was found to be higher than those of the other antibiotics tested. In dogs, however, the rate of urinary excretion of ceftezole was nearly the same as that of cefazolin and higher than those of cephaloridine and cephalothin. The biliary excretion of ceftezole in rats and dogs was much higher than those of cephaloridine and cephalothin, but lower than that of cefazolin. Tissue distribution of ceftezole in rats was compared with that of the other antibiotics by intramuscular and intravenous administration. The initial level of ceftezole in the kidneys was found to be substantially higher than those of the other antibiotics. The initial level of ceftezole in the liver and lungs was also slightly higher than those of the other drugs when administered intramuscularly. Tissue levels of ceftezole were somewhat lower than those of cefazolin in rabbits after intravenous administration. Ceftezole attained a higher maximum level in rat lymph by intramuscular administration than the other antibiotics tested. The maximum
concentration of ceftezole present in the exudate in the rat inflammatory pouch was higher than that of cefazolin. In rabbits with cerebrospinal meningitis induced by infection of Streptococcus pyogenes, the level of ceftezole in the cerebrospinal fluid was several times higher than that in normal rabbits. The serum level and urinary excretion of ceftezole was examined in 6 healthy male volunteers after intramuscular administration of a single dose of 500 mg. Ceftezole attained a mean maximum serum level of 22.9 μg/ml 30 minutes after administration and disappeared from the blood in about 6 hours. It was excreted rapidly in the urine. The concentration in 1-hour urine was the highest (mean level: 2, 667 μg/ml) and the total excretion rate was 92.6%. No metabolites with antimicrobial activity were observed in the urine. No changes in the pattern of plasma level and urinary excretion and no accumulation in the tissues were observed after repeated intramuscular administration of 20 mg/kg of ceftezole in rabbits, 26 times, for 14 days.

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Efrotomycin is a narrow spectrum antibiotic. Among the genera tested for susceptibility in vitro it is most active against isolates of Moraxella, Pasteurella, Yersinia, Haeniophilus, Streptococcus and Corynebacterium. The drug is as active by oral administration as by the subcutaneous route. Blood levels rise rapidly to high concentrations, after oral dosing, and are prolonged. Two peaks occur which may indicate biliary excretion and reabsorption. Urinary excretion is minimal. The high blood concentrations explain, in part, the in vivo activity against pathogens such as Bordetella bronchiseprica which are relatively insensitive in vitro. Oral activity of efrotomycin is an advantage over the related antibiotics, X-5108 and mocimycin.

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Isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniaeand Proteus mirabilisere incubated in the presence of inhibitory concentrations of cephalothin. After destruction of the antibiotic, there was a lag phase before Saureus an to proliferate again.
When similar experiments were conducted with E. coli, K. pneumoniae, and P. mirabilis, no lag phase was observed. This data suggests that the inhibitory activity of cephalosporins may be different for gram-positive cocci and gram-negative bacilli.

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Bleomycin (10^-6M) has been tested in Allium cepa L. meristems which are formed by a proliferating cell population growing under steady state conditions. Chromosome breaks were apparently induced by the antibiotic in cells in G₂ period since anaphases with chromatid
breaks were formed at a time shorter than G₂ + prophase duration. Stimulation of entrance of G₂ cells into mitosis is suggested both by an increase in the frequency of early prophases and by the study of waves of prophases in a synchronous subpopulation labelled by caffeine.
Progression of other mitotic phases was unaffected. Nucleologenesis rate was increased by the antibiotic in a fashion resembling protein synthesis inhibitors. Protein synthesis is inhibited by 10^-6 M bleomycin to the same extent as 4 × 10^-6 M anisomycin. Both facts suggest that bleomycin has a direct inhibitory effect on protein synthesis in meristems.
Given the nucleologenesis sensitivity to nucleolar RNA inhibition it is suggested that the antibiotic activity on nucleolar transcription is mediated through DNA.

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Gel filtration has shown that there are considerable differences between the metal complexes of bleomycin A₂ and B₂ with indium, cobalt or copper. Differences in the rates of formation of the complexes have also been found and it is thought that these effects are due to a difference
in co-ordination between the metals and the bleomycin. The co-ordination changes are thought to be the cause of the differences in in vivo distribution of metal bleomycin complexes found in the radiodiagnosis of tumours. The ease of formation of the copper or cobalt complexes is suggested as a possible mechanism for the inhibition of the attack of DNA by bleomycins.

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