A new nucleotide antibiotic, phosmidosine was isolated from a culture filtrate of a newly isolated streptomycete identified as Streptomyces sp. RK-16. HRFAB-MS and elemental analysis established the molecular formula of C₁₆H₂₄N₇O₈P. ¹H, ¹³C and ³¹P NMR indicated the presence of a methyl phosphate group and UV spectra were similar to those of 8-hydroxyadenosine. The antibiotic inhibited spore formation of Botrytis cinerea at the concentration of 0.25 μg/ml.

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Synerazol, a new antifungal antibiotic, was isolated from cultured broth of Aspergillus fumigatus SANK 10588. The structure was determined based on NMR and mass spectral evidences. Synerazol was found to be a related substance to pseurotin A. Synerazol was active against Candida albicans and other fungi, and showed marked synergistic activity with azole-type antifungal agents.

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Furaquinocins C, D, E, F, G and H, congeners of furaquinocins A and B, were isolated from the culture broth of Streptomyces sp. KO-3988 and their structures have been determined on the basis of their spectroscopical and chemical properties. These antibiotics showed cytocidal activities against HeLa S3 and B16 melanoma cells in vitro.

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A new antibiotic, dioxamycin (1) was isolated from the culture broth of the strain MH406-SF1, which was closely related to Streptomyces xantholiticus. This antibiotic was purified by countercurrent chromatography, column chromatography and preparative HPLC. The molecular formula of 1 was determined to be C₃₈H₄₀O₁₅ by HRFAB-MS. The structure was determined by spectral analysis of 2D NMR; ¹H-¹H COSY, ¹³C-¹H COSY, long range ¹³C-¹H COSY (HMBC) and NOESY. The antibiotic is active in vitro against Gram-positive bacteria and some tumor cells. Dioxamycin is a benz[α]anthraquinone antibiotic related to capoamycin.

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Maduropeptin, a complex of new macromolecular antitumor antibiotics, is a metabolite of Actinomadura madurae H710-49. The active components maduropeptins A₁, A₂ and B are acidic chromopeptides with MW of around 22, 500 and composed of 14 types of amino acids and an unstable chromophore. The antibiotics are active in vitro against Gram-positive bacteria and highly cytotoxic to tumor cells. They produced significant prolongation of survival time of mice implanted with P388 leukemia and B16 melanoma.

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Preparation of cephaloosporins bearing a 1, 3-dithietane ring attached to the C-3 position using intramolecular rearrangement are described. The diastereoisomers (6a-I and 6a-II) were separated by silica gel column chromatography. These 3-[4-(carbamoyl carboxymethylene)-l, 3-dithietan-2-yl]cephems showed comparable activity against Gram-negative bacteria to that of ceftazidime.

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The syntheses and biological activities of new 7-β-[(Z)-2-(2-amino-4-thiazolyl)-2-hydroxy-iminoacetamido]-3-(l, 3-dithiolan-2-yl)-3-cephem-4-carboxylic acid (YM-22508, 1a), 7-β-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-(1, 3-dithiolan-2-yl)-3-cephem-4-carboxylic acid (YM-16457, 1d) and their prodrug-type esters are described. Among them, YM-22561 (1c), the 1-acetoxyethyl ester of 1a, showed good in vivo efficacy in mice against infections of Staphylococcus aureus Smith, Streptococcus pyogenes S 23 and Escherichia coll NY-17 and a long plasma T_1/2 in mice.

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Liblomycin (NK313) is a novel derivative of bleomycin (BLM) and peplomycin (PEP). The cell kill kinetics of NK313 on rat ascites hepatoma AH66 were compared with those of PEP. NK313 induced intracellular DNA cleavage and arrested cell cycle progression at the G₂ phase similarly to PEP. The cytocidal effect of NK313, however, was found to be different from that of PEP as described below: 1) The dose-survival curve for cells exposed to PEP for 1 hour was upward concave, whereas in case of NK313, the survival curve was linear. PEP was more effective to AH66 than NK313 at lower concentration, but at higher concentration, NK313 was much more effective. 2) The time-survival curve for cells treated with either NK313 or PEP was biphasic. NK313, however, did not induce temporary resistance of AH66 cells to NK313, while PEP induced resistance to PEP. 3) NK313 was effective against the cells which became temporarily resistant to PEP by the treatment of PEP. These differences suggest that NK313 might be of value to treat PEP-insensitive tumor cells.

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A β-lactamase was purified from Klebsiella oxytoca strain GN10650. The enzyme was chromosomally-mediated and gave a single protein band on polyacrylamide gel electrophoresis. Its pI was 5.34 and its MW was approximately 27, 000. The optimal pH and temperature were about 7.0 and 50°C, respectively. The specific activity of the enzyme was 1, 207 units per mg of protein for hydrolysis of penicillins and cephalosporins, including cefuroxime, cefotaxime, and aztreonam. The enzyme activity was inhibited by p-chloromercuribenzoate, iodine, ferrous ion, and by clavulanic acid. Rabbit antibodies raised against the purified K. oxytoca enzyme showed no cross-reactivity in neutralization tests with β-lactamases produced by other species of Gram-negative bacteria.

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Pharmacokinetic properties of WF-3681 and FR-62765 in rats were examined. FR-62765 showed higher peak concentrations in the plasma and higher concentrations in the sciatic nerve than WF-3681 when each compound was administered orally to rats. We therefore evaluated FR-62765 in rats with diabetic neuropathy. As a result, FR-62765 at 32mg/kg/day administered for 3 weeks to streptozotocin-induced diabetic rats significantly prevented the accumulation of sorbitol in the sciatic nerve and the reduction of motor nerve conduction velocity in the tail. From these results it was concluded that the aldose reductase inhibitor FR-62765 might be a useful drug for diabetic neuropathy.

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