Herbimycin, a new antibiotic, was isolated from the fermentation broth of Streptomyces hygroscopicus strain No. AM-3672, a soil isolate. The molecular formula of herbimycin was determined to be C₃₀H₄₂N₂O₉. Herbimycin was found to have potent herbicidal activity against most mono- and di-cotyledonous plants, especially against Cyperus microiria STEUD. However, Oryza sativa showed strong resistance to herbimycin.

抄録全体を表示

Antibiotic PS-5¹⁾ is a new β-lactam antibiotic isolated from fermentation broths of Streptomyces sp. strain A271. The strain was considered to be a new subspecies of Streptomyces cremeus and the name, Streptomyces cremeus subsp. auratilis, was proposed. Fermentative production, isolation and physico-chemical properties of PS-5 are described.

抄録全体を表示

PS-5, a new β-lactam antibiotic¹⁾, has relatively potent antimicrobial activity against Gram-positive and Gram-negative bacteria, especially the Enterobacter groups, Serratia marcescens, the Proteus groups and Klebsiella pneumoniae. The activity of PS-5 against many β-lactamase-producing organisms is greater than that of cefoxitin or cefazolin. PS-5 has good therapeutic activity in mice infected with Staphylococcus aureus Smith or Enterobacter cloacae 45.

抄録全体を表示

PS-5 was shown to have synergistic activity in combination with other β-lactam antibiotics and it markedly decreased the minimum inhibitory concentration values of ampicillin or cephaloridine with a β-lactamase-producing Proteus vulgaris strain on agar plates. The synergistic activities were also shown in bactericidal activity in liquid medium. PS-5 was shown to be inhibitory against an extracted β-lactamase of P. vulgaris.

抄録全体を表示

The screening of soil actinomycetes for β-lactamase inhibitors is described. Using a plate test a number of strains of Streptomyces were found to produce β-lactamase inhibitory activity designated olivanic acid complex. Factors affecting the production of this complex by Streptomyces olivaceus ATCC 21379 are reported. The complex showed antibacterial activity and also inhibited a number of different types of β-lactamase in a progressive manner. Certain ampicillin-resistant bacteria are rendered sensitive to ampicillin in the presence of olivanic acid complex at a concentration which alone did not inhibit growth.

抄録全体を表示

The olivanic acids MM 4550, MM 13902 and MM 17880 are members of a new family of β-lactam antibiotics. An isolation and purification process utilising ion-pair extraction and ion-exchange chromatography is described and the metabolites are characterized by physico-chemical and biological properties.

抄録全体を表示

On examining the structures of the antibiotics tridecaptins B and C, the constituent amino acids were separated and their chiralities were determined. The constituent fatty acids were identified by gas chromatography and mass spectrometry. Cleavage with N-bromosuccinimide and sequential analysis by EDMAN degradation demonstrates the sequence of the C-terminal side of tridecaptins B and C. Deacylation with polymyxin acylase of tridecaptin B and successive EDMAN degradation revealed the sequence of the N-terminal side of tridecaptin B. Finally partial acid hydrolysis on tridecaptin C clarified the sequence of the N-terminal side of tridecaptin C.

抄録全体を表示

By high performance liquid chromatography, cerexin B was separated into four components (B₁, B₂, B₃ and B₄), cerexin D into four components (D₁, D₂, D₃ and D₄), tridecaptin A into two components (A_α and A_β), tridecaptin B into four components (B_α, B_β, B_γ, and B_δ) and tridecaptin C into three components (C_α1, C_α2 and C_β1). All components were preparatively isolated, and their fatty acid and amino acid compositions determined for structural elucidation.

抄録全体を表示

Synthesis and in vitro antimicrobial activity of a number of cephalosporins related to cefmetazole (CS-1170) are described.

抄録全体を表示

A new antitumor antibiotic, named auromomycin, was isolated from the culture broth of Streptomyces macromomyceticus, a macromomycin-producing strain. The antibiotic was recovered from the culture filtrate by salting out with ammonium sulfate and further purified by successive application of ion-exchange chromatography on Amberlite IRA-93 (Cl form) and DEAE-Sephadex (OH form), Gel filtration on Sephadex G-50 and hydrophobic chromatography on Octyl-Sepharose CL-4B. The antibiotic is an acidic polypeptide with a molecular weight of 12, 500 and an isoelectric point of pH 5.4 and consists of 16 different amino acids. It has characteristic absorption maxima at 273 nm and 357 nm in the ultraviolet spectrum and two minima at 280 nm and 350 nm in the optical rotatory dispersion spectrum. Auromomycin exhibits antibacterial activity not only against Gram-positive bacteria, but also Gram-negative bacteria. Antitumor activities of auromomycin were revealed against EHRLICH ascites carcinoma, ascites sarcoma 180, L1210 leukemia and LEWIS lung carcinoma.
Auromomycin was found to be converted into macromomycin by adsorption chromatography on Amberlite XAD.

抄録全体を表示

Macromomycin (MCR) is a polypeptide antitumor antibiotic isolated from the culture broth of Streptomyces macromomyceticus. Antitumor activities of MCR were examined against three different tumor systems, i.e., EHRLICH ascites carcinoma, L1210 leukemia and LEWIS lung carcinoma. Daily intraperitoneal treatment with MCR for 5 days showed a strong inhibition against EHRLICH ascites carcinoma. Both single and repeated intraperitoneal
injections of MCR were effective over a wide dose range against intraperitoneally inoculated L1210 leukemia and MCR intravenously administered was also active against intravenously inoculated L1210 leukemia. Daily local subcutaneous injections of MCR produced the prolongation of life span of mice to which LEWIS lung carcinoma was subcutaneously inoculated with some cured mice, but daily intraperitoneal injections of MCR showed no activity. Single intravenous administration of MCR inhibited early LEWIS lung carcinoma, but not advanced LEWIS lung carcinoma. The combination of MCR with aracytidine, or cyclophosphamide showed a synergistic activity against L1210 leukemia. MCR was not inactivated by treatment with serum, although neocarzinostatin was markedly inactivated by the same treatment.

抄録全体を表示

The antifungal antibiotic, prumycin, was studied for antitumor activity against several tumor systems. It was found to possess potential antitumor activity against a well-established mouse mammary adenocarcinoma in C3H/He mice. It was also active in prolongation of the lifespan of mice bearing P-388 lymphocytic leukemia. Moreover, prumycin did not depress the white blood cell counts in the mouse peripheral blood. However, severe alopecia was observed in mice treated with this agent at dosage levels near the LD₅₀.

抄録全体を表示

The ¹³C-NMR spectra of 1-N-[(S)-4-amino-2-hydroxybutyl]kanamycin A (butikacin) (Fig. 1, 1b) and some of its related compounds have been recorded and are tabulated, assigned and discussed. The chemical shifts of many of the carbon nuclei are shown to be reasonably invariant amongst this series of compounds. A procedure is described for the determination of the (R, S)-epimer ratio of kanamycin A derivatives which have N-substituted groups containing a chiral centre.

抄録全体を表示

Mocimycin was converted to the acylesters by selective acylation of the hydroxyl group of the 4-hydroxy-1-methyl-2(1H)pyridinone moiety. Subsequent N-methylation at the nuclear nitrogen and removal of the protective group from the resulting reaction products afforded aurodox. Mono-O-acetylmocimycin and several analogous aurodox esters thus prepared possess antibacterial activity in vitro and growth-promotion properties in poultry. Esters of aurodox involving the hydroxyl group of the 4-hydroxy-1-methyl-2(1H)pyridinone moiety are activated. Accordingly, acetic acid treatment of the aurodox esters generates O-acylgoldinamines which undergo transacylation furnishing N-acylgoldinamines. Alternatively, N-acylgoldinamines can be prepared by selective mono-O-arylsulfonylation of aurodox, liberating O-arylsulfonylgoldinamine by treatment with acetic acid followed by N-acylation and removal of the protective arylsulfonyl group. A third approach to N-acylgoldinamines consists in direct N-acylation of goldinamine itself which is prepared by acetic acid treatment of aurodox. None of these derivatives prepared, however, exhibited significant antimicrobial or growth-promoting properties, suggesting that the goldinonic acid moiety, or a closely related derivative thereof, is required for biological activity.

抄録全体を表示

The thermal rearrangement of antifungal antibiotic 1, isolated from Polyangium cellulosum var. fulvum, to cycloheptadiene derivative 2 is described.

抄録全体を表示

Among the new aminoglycoside antibiotic family of fortimicins, components A, C and D have higher activity compared to their 4-N-deacylated components B and KE. Synthesis and antibacterial activities of 4-N-acyl- and 4-N-alkyl-fortimicin B derivatives are described. 4-N-Acylfortimicin B's, which are relatively unstable in alkaline conditions, were converted to stable 4-N-alkyl derivatives with diborane. The activity is greatly affected by the 4-N-substituents,
and the presence of hydrophilic group(s) is necessary to confer activity on the derivatives. 4-N-(2-Aminoethyl)-, 4-N-(4-amino-2-hydroxybutyl)- and 4-N-(2-hydroxy-4-methylaminobutyl)-fortimicin B are the most potent compounds among them.

抄録全体を表示

Feeding experiments and chemical degradations have shown that D-[1-¹⁴C, 2-³H]-and-[1-¹⁴C, 6-³H] glucosamine, L-[ureido-¹⁴C] citrulline, L-[guanidino-¹⁴C] arginine and L-[¹⁴CH³] methionine specifically label the glucosamine moiety, the urea carbonyl and the N-methyl group of the antibiotic streptozotocin, respectively. Feeding these precursors in amounts of 5-10μmoles per 100 ml of culture medium under conditions where the fermentation yielded approximately 20μmoles of streptozotocin in 24 hours gave incorporation rates which approached 40%. Upon feeding 100μmoles of either D-[1-^14C] glucosamine or L-[ureido-¹⁴C] citrulline they were incorporated into newly synthesized streptozotocin essentially without dilution by endogeneous precursors. D-[1-¹⁴C, 6-³H] Glucosamine was incorporated without change in T/C ratio while 20% of the tritium was lost from D-[1-¹⁴C, 2-³H] glucosamine, suggesting the possibility that D-glucosamine can partially equilibrate with D-fructose prior to its incorporation.

抄録全体を表示

Sporamycin, an antitumor antibiotic, primarily inhibited DNA synthesis, while RNA and protein synthesis were not significantly affected in HeLa S3 cells. The antibiotic also caused strand scission of cellular DNA. However, the effects were not observed when the cells were incubated at 0°C before washing and subsequently incubated at 37°C. The Tm of calf thymus DNA decreased when incubated with sporamycin in vitro. Sporamycin did
not affect DNA synthesis in vitro catalyzed by partially purified DNA polymerase α, β, and γ derived from EHRLICH ascites cells.

抄録全体を表示

Streptomyces griseoviridus produces in addition to etamycin several related compounds which can be separated by partition chromatography. One of these has been characterized by amino acid analysis and mass spectrometry and shown to have the same structure as etamycin except for replacement of the hydroxyproline residue by proline. Evidence was obtained for additional congeners similarly related to etamycin by amino acid exchange. The relative proportions of such congeners produced by S. griseoviridus depends upon the medium in which the culture is grown. Certain amino acids support good yields of the metabolites and the culture appears to be steered towards the synthesis of congeners containing such amino acids.

抄録全体を表示

The binding of [¹⁴C]bicyclomycin to whole cells of E. coli and to the inner membrane proteins was inhibited by dithiothreitol and 2-mercaptoethanol. The reactivity of the drug with the sulfhydryl group was further studied, using methanethiol as a model compound. The kinetics revealed that the reaction was of pseudo-first-order in excess of thiolate anion. Analysis with gas chromatography-mass spectrometry showed that the main product was an adduct of thiol with bicyclomycin in an equal molar ratio. The structure of the adduct was determined by ¹H-NMR spectrometry, showing that thiolate attacked the olefinic double bond of the antibiotic. 3'-Acyl derivatives of bicyclomycin did not significantly affect the binding of [¹⁴C] bicyclomycin to inner membrane proteins ofE. coli. The results suggested that 4, 5-double bond hydrocarbons and 3'-hydroxy group of bicyclomycin participate in the binding to E. coli inner membrane proteins, which are presumably the receptors of the antibiotic. The olefinic double bond seems to be the active center of bicyclomycin, reacting with the sulfhydryl group of the receptor protein, although the whole molecule is needed for the activity.

抄録全体を表示

The effects of primycin were investigated on the alkali-cation transport of human erythrocytes and on the electric conduction of bimolecular lipid membranes. In the concentration range of 3•10^-6-10^-5M primycin increased the permeability of erythrocytes to alkali-cations according to the sequence Cs⁺>Rb⁺-K⁺»ÓÓNa⁺, while the conductance of the negatively charged phosphatidylserine bimolecular lipid membrane increased by 2-3 orders of magnitude. The resistance-lowering effect of primycin strongly depended on the cationic species applied and a selectivity order Na⁺>K⁺>Rb⁺>Cs⁺ was found. A possible mechanism of the primycin-membrane interaction is suggested on the basis of experimental data.

抄録全体を表示