A number of strains of Oidiodendron truncatum was shown to produce a new antibiotic, PR-1350, which was isolated in the form of an amorphous powder either directly or via a crystalline monomethanolate, PR-1381, which in solution is reconverted to the parent compound. The antibiotic inhibits a broad spectrum of Gram-positive and Gram-negative bacteria in vitro, and has been shown to be active against P-388 lymphocytic leukemia in mice. Biosynthetic considerations based on the results of [1-¹³C]acetate incorporation indicate that the antibiotic is a diterpene of the clerodane type.

抄録全体を表示

A novel enzyme inhibitor against RNA-directed DNA polymerase of avian myeloblastosis virus was produced by an isolate of a new streptomycete for which the name Streptomyces retrostaticus is proposed. This enzyme inhibitor, which was named retrostatin, did not inhibit DNA-directed DNA polymerase of Escherichia coli and DNA-directed RNA polymerase of Ehrlich ascites tumor cells. Retrostatin was produced by the microorganism together with streptonigrin. These two substances were extracted from the culture broth with ethyl acetate at acidic pH. Retrostatin is an acidic pH indicator and the free acid was recovered as a red powder. Retrostatin had weak antibiotic activities against Gram-positive bacteria and yeasts.

抄録全体を表示

A new polyene macrolide antifungal antibiotic, named tetrafungin, was isolated from the cultured mycelium of a Streptomyces strain. Fermentation, isolation, physico-chemical and biological properties of the antibiotic are described. Its UV absorption spectrum and its physico-chemical characteristics place this antibiotic in the group 2.2.2.3 of the BERDY classification.

抄録全体を表示

Tetrafungin, a new polyene macrolide antibiotic, is produced by a Streptomyces strain identified as a new subspecies of Streptomyces albulus and named Streptomyces albulus subsp. tetrafungini. Tetrafungin and nystatin have been investigated and compared by HPLC. It has been demonstrated that tetrafungin and nystatin differ qualitatively in, at least, one component, and quantitatively in their relative amounts of common components.

抄録全体を表示

The structure of fermentation product A 19009 was reinvestigated by ¹³C and ¹H NMR spectroscopy and established by independent synthesis to be N²-L-alanyl-N3-fumaramoyl-L-2, 3-diaminopropanoic acid (2), i. e. a structure isomeric with the originally proposed structure 1. In contrast to 1 which also was synthesized, 2 has a very low activity against Trichomonas vaginalis.

抄録全体を表示

The peptide antibiotic edeine F produced by Bacillus brevis Vm₄, one of the components of edeine antibiotics complex, was isolated from a fermentation broth and was also obtained by amidination of edeine D. Edeine F is composed of amino acids: (S)-β-phenyl-β-alanine, (S)-isoserine, (S)-2, 3-diaminopropionic acid, (2R, 6S)-diamino-(7R)-hydroxyazelaic acid, glycine and a polyamine guanidylspermidine. Enzymatic degradation of antibiotic with carboxypeptidase B, dinitrophenylation of edeine and of its enzymatic degradation products and synthesis of edeine F from edeine D of known structure permitted to postulate the chemical structure for edeine F.

抄録全体を表示

The majority of the 84 protons in the ¹H NMR spectrum of thiostrepton at 300 MHz were unambiguously assigned on the basis of double resonance experiments under different conditions of solvent, temperature and ²-exchange by comparison with the known crystal structure determined by ANDERSON et al. ¹⁾ Evidence is presented to suggest that the side chain, the nature of which remained undefined on X-ray analysis, is comprised of two dehydroalanine residues which supports the conclusions reached by TORT et al.²⁾ on the basis of ¹³C NMR spectroscopy. These two residues are missing in thiostrepton A₂, a minor artifact. All available ¹H NMR evidence suggests thiostrepton to have a similar conformation in deuterochloroform solution to that found in the crystal form.

抄録全体を表示

On the basis of ¹H and ¹³C NMR evidence, the structures of two series of the Highly modified sulfur-containing peptide antibiotic thiopeptin were elucidated.

抄録全体を表示

A detailed ¹³C NMR study of thiostrepton and two series of thiopeptin components is consistent with their proposed structures and allows many unequivocal assignments to be made.

抄録全体を表示

The synthesis and in vitro activity of the 7-[O-substituted oxyiminoacetamido]cephalosporins (I) without substitution at 3-position of a cephem nucleus are described. Effect of changing the oxime O-substituents (R¹) with various functional groups in the 7-acyl residue on antibacterial activity was examined. Against Gram-positive bacteria, cephems with hydrophilic functions in the R¹ moiety such as hydroxyethyl, aminoethyl and carboxymethyl groups showed decrease of the activity, while cephems with lipophilic functions such as cyanomethyl, methylthiomethyl and halogenoethyl groups exhibited increase of the activity. However, influence of the substituents (R¹) on activity against Gram-negative bacteria was observed to be relatively independent of the nature of their functional groups.

抄録全体を表示

By applying the synthetic process reported in our previous paper, we synthesized new carbapenems having various (substituted) thio and alkoxy groups at the C(3) position and 1-hydroxy-1-methylethyl and analogous groups at the C(6) position with cis- and trans-stereochemistry; the in vitro antibacterial and β-lactamase inhibitory activities of these new carbapenems were examined. Compared to C-19393 H², some of these compounds (e.g., 11A-a-3-5) showed improved in vitro antibacterial activity especially against Pseudomonas aeruginosa; they showed a strong β-lactamase inhibitory activity as well. Two noteworthy effects of substituent variation at the C(6) position on the activities were observed: 1) the trans-configuration caused a definite loss; and 2) introduction of 1-hydroxycyclobutyl and 1-hydroxy-1-methylpropyl groups in place of the 1-hydroxy-1-methylethyl group caused a diminution. The carbapenem (13A-a-2)with an alkoxy group at the C(3) position had a marked decrease in activity compared to the corresponding thio-substituted carbapenem (11A-a-12).

抄録全体を表示

A general screening procedure is described which allows the rapid determination of the susceptibility of naturally occurring carbapenem antibiotics to renal dehydropeptidase-I at the broth level. The procedure is based on the incubation of carbapenem-containing solutions with dehydropeptidase-I and the subsequent assay of residual β-lactamase-inhibiting/inactivating activity of carbapenems by means of a plate technique using the chromogenic β-lactamase substrate PADAC.

抄録全体を表示

A method for measuring 4'-O-tetrahydropyranyladriamycin (THP) and its metabolites in biological samples are described. By reversed-phase high performance liquid chromatography using fluorescence detection, THP and its metabolites were all separated on a single chromatogram within 18 minutes. A linear calibration curve was obtained up to 2, 000 ng/ml of THP in plasma. The recovery of THP in the analysis was more than 95% above 5 ng/ml and 87.1% even at 1.25 ng/ml. Thus the lower limit was 1.25 ng/ml in biological samples. Blood levels and urinary excretion in mice and dogs were satisfactory measured by this analytical method.

抄録全体を表示

Various microorganisms were tested for capability to hydroxylate of ML-236B at the 3β-position. As the result, it was found that this ability was limited to a small group of microorganisms, mainly Zygomycetes in fungi, and Nocardia in actinomycetes.

抄録全体を表示

Ascofuranone (AF) has antitumor protective property on experimental tumors. We examined the action of AF on lymphoma L5178Y to explore the mechanism of the antitumor activity. AF completely prevented the growth of L5178Y at 25 μg/ml cytostatically. The compound exhibited general inhibitory effects on the macromolecular syntheses. Among them, protein synthesis was most severely inhibited by AF and to the same extent as by cycloheximide. AF, however, did not affect protein synthesis by cell-free system even at 2 mg/ml. Although AF inhibited the incorporation of [¹⁴C]acetate into total acid precipitable products only slightly, the synthetic pattern of simple lipids from [¹⁴C]acetate was significantly changed. Especially, the incorporation of [¹⁴C]acetate into squalene was almost completely blocked at 25 μg/ml. The incorporation of [¹⁴C]acetate into triglyceride was inhibited and that into cholesterol was enhanced. Concerning the diglycerides, the incorporation of [¹⁴C]acetate was enhanced and that of [³H]glycerol was inhibited. The incorporation of [³H]glycerol and [³H]mevalonate into the intact cell was significantly inhibited as compared with [¹⁴C]acetate. As those effects were not observed with cycloheximide, they were suggested to be characteristic of AF. AF inhibited hypotonic hemolysis. In contrast, hemolysis by deoxycholate was stimulated. Possible mechanism of the antitumor activity of AF is discussed.

抄録全体を表示

Aclacinomycin A inhibited the in vitro conversion of phage φX174 single-stranded DNA to the replicative form DNA. DNA synthesis was inhibited by 50% in the presence of 15μM aclacinomycin A. The inhibition was competitive with respect to template DNA (K_i=13 μM) and was reversed by addition of Escherichia coli cell extracts. Short complementary strands approximately one-third of unit length molecule were synthesized in the presence of 15 μM aclacinomycin A. The data suggest that aclacinomycin A may inhibit the process of φX174 DNA chain elongation by a direct interaction with the E. coli host enzymes.

抄録全体を表示

The penicillin binding proteins (PBSs) of Bacteroides fragilis, a clinically important Gram-negative rod, were studied. Four PBPs were detected by polyacrylamide gel electrophoresis/ fluorography, PBP 4 (molecular weight, 35, 000) being a minor PBP. The PBP pattern was thus different from that of the Enterobacteria and Pseudomonads. Antibacterial activity of β-lactam antibiotics was associated with binding to PBP 1 (molecular weight, 100, 000), 2 (molecular weight, 86, 000) and 3 (molecular weight, 68, 000). Binding to PBP 2 was associated with filamentation while binding to PBP 1 resulted in cell lysis.

抄録全体を表示