The antitumor effects of kidamycin were studied on experimental animal tumors. On EHRLICH ascites carcinoma, kidamycin was remarkably effective but the effect on leukemia SN-36 was not excellent. A slight efficacy of kidamycin on leukemia L1210 was observed. On Sarcoma-180, a good and characteristic result was obtained at a dose of 7 mg/kg, and 4 of 10 treated mice survived without tumors. Kidamycin was also effective on NF-sarcoma and YOSHIDA sarcoma.

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In attempts to reduce the toxicity and to enhance the activity of kidamycin many efforts have been made, and acetyl kidamycin was thus obtained in a pure crystalline state as one of the derivatives of kidamycin. It exsists as yellow needle crystals, and has three acetyl groups in the molecule. Acetyl kidamycin showed a lower toxicity than that of kidamycin, and its LD₅₀ value was about 200 mg/kg intravenously.

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The peptide antibiotic sporangiomycin specifically inhibits protein synthesis when added to growing cultures of Bacillus subtilis. A study on the reactions for bacterial protein synthesis in cell-free systems has shown that sporangiomycin interferes with specific reactions responsible for peptide-chain elongation, while it has no effect on peptide chain initiation. The primary action of the antibiotic appears to be on the 50 S ribosomal subunit. This is suggested by the observation that ribosomes pre-treated with sporangiomycin are inactive in protein synthesis and that the inhibition can be overcome by an excess of 50 S subunits.
Furthermore, ³⁵S-labelled sporangiomycin binds specifically to 50 S particles. Step-wise release of groups of ribosomal proteins by treatment with increasing concentrations of LiCl has shown that a specific fraction (the 1.3-1.7 M LiCl split proteins) is essential for antibiotic binding to the 50 S particle. It is hypothesized that sporangiomycin inhibits protein synthesis by binding to a ribosomal multimolecular site of the utmost importance in the process of peptidechain elongation.

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Bicyclomycin is a new antibiotic obtained from the culture filtrate of Streptomyces sp. WS 4545 which was identified as a new species and given the name Streptomyces sapporonensis. Its elementary analysis and mass spectroscopic measurement suggest that the molecular formula is C₁₂H₁₈N₂O₇. There is no specific ultraviolet absorption. Bicyclomycin is active against Gramnegative bacteria, especially Escherichia coli, Klebsiella, Shigella and Salmonella species, and has no cross resistance with the usual antibiotics. It has low toxicity in mice.

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The structure of bicyclomycin, a novel antibiotic, was largely elucidated by nuclear magnetic resonance spectroscopy and established finally as 8, 10-diaza-6-hydroxy-5-methylene-l-(2'-methyl-1', 2', 3'-trihydroxy-propyl)-2-oxabicyclo [4, 2, 2] decan-7, 9-dione by X-ray crystallographic diffraction analysis. A number of its acyl derivatives were prepared and studied biologically. The relationship between the structure of the acyl derivatives and the rate of urinary excretion was also examined.

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Bicyclomycin is a new antibiotic active against Gram-negative bacteria such as Escherichia coli, Klebsiella, Shigella, Salmonella, Citrobacter, Enterobacter cloacae, and pathogenic group of Neisseria, but inactive against Proteus, Pseudomonas aeruginosa, and Gram-positive bacteria. This antibiotic shows no cross-resistance with any of the known antibacterial drugs such as streptomycin, kanamycin, chloramphenicol, tetracycline, ampicillin and nalidixic acid. Its activity is bactericidal, with little varieties of MIC values under various experimental conditions. Bicyclomycin is not degraded in culture broths of sensitive and resistant organisms or rat tissue homogenates, and the extent of binding with serum protein is very low. It was effective subcutaneously in curing E. coli experimental infections in mice with strains resistant to the usual antibiotics.

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Bicyclomycin, a new antibiotic active against Gram-negative bacteria and having a unique chemical structure, was investigated for its absorption, excretion and tissue distribution. Bicyclomycin was intramuscularly administered to mice, rats, rabbits and dogs at a single dose of 50 mg/kg. Although the mean peak levels in the blood and serum differed with animal species, the values were found to be fairly high. Seventy% or more of the given dose were recovered in the 24-hour urine samples.
A relatively long half-life of bicyclomycin was observed as compared with that of ampicillin, when both antibiotics were administered intravenously to rabbits at a single dose of 50 mg/kg.
The results of the study on the biliary excretion in rats showed its low excretion rate after a single intramuscular dose of 50 mg/kg. When a single intramuscular dose of 100 mg/kg was given to rats, bicyclomycin was well distributed in various tissues, and the highest concentration was observed in the kidney.
In human volunteers, mean peak serum levels were 18.0 and 31.9 meg/ml at the first 30 minutes and 1 hour when dosed intramuscularly at 500 mg and 1 g, respectively. Urinary excretions of bicyclomycin were relatively high, i.e. 96.2 and 94.8% at a dose of 500 mg and 1 g, respectively, during 24 hours. No metabolite possessing antimicrobial activity except bicyclomycin was found in the urine samples from the human volunteers. When given orally, bicyclomycin was absorbed to a certain extent in rats, but only to a limited extent in human volunteers.

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