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Biomedical subjects

H Naganawa

Publications and source records attributed to H Naganawa.

At least 19 recordsLinked to original sources

Inhibitory effects of polyethers on human immunodeficiency virus replication.

We examined the inhibitory activities of 10 polyether antibiotics on human immunodeficiency virus (HIV) type 1. These compounds caused concentration-dependent inhibition of HIV replication in primary infected cultures of human T-lymphoblastoid H9 cells. The ratio of 50% effective concentrations for cellular cytotoxicity (MTT assay) to antiviral activity (reverse transcriptase assay) was over 5. Anti-HIV activity was also observed in cultures of monocytic lineage U937 cells chronically infected with HIV.

Anti-Bacterial Agents

Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. II. Structure determination of benastatins A and B.

Benastatins A and B, new inhibitors of glutathione S-transferase, have been isolated from the culture broth of Streptomyces sp. MI384-DF12. By X-ray crystallography, benastatin A was determined to be 8,13-dihydro-1,7,9,11-tetrahydroxy-13-dimethyl-8-oxo-3-pentyl- benzo[a]naphthacene-2-carboxylic acid. The structure of benastatin B was elucidated by NMR studies.

Benz(a)Anthracenes

Production of new anthracycline antibiotics 1-hydroxy-oxaunomycin and 6-deoxyoxaunomycin by limited biosynthetic conversion using a daunorubicin-negative mutant.

A limited biosynthetic conversion of some known anthracyclinones using a specific daunorubicin-nonproducing mutant provided four new anthracycline antibiotics: 1-Hydroxy-10-methoxycarbonyl-13-deoxocarminomycin; 1-hydroxy-13-deoxocarminomycin; 1-hydroxyoxaunomycin and 6-deoxyoxaunomycin. Their isolation and purification from bioconversion broth, structural determination and antitumor activities against leukemic L1210 cells are described.

Animals

Photochemically obtained N-demethyl derivatives of anthracyclines.

New N-monodemethyl and N-didemethyl derivatives were obtained from seven N-dimethylamino sugar (rhodosamine)-containing anthracyclines by photochemical reaction and their in vitro bioactivities against L1210 cell culture were compared with those of their N-dimethyl parent compounds. N-Demethyl derivatives obtained from betaclamycin T (7-O-rhodosaminyl-beta-rhodomycinone) were much more cytotoxic while those from the other six antibiotics were rather less active as compared with their parent compounds. The N-demethylation also gave a considerably greater decrease in the inhibitory activity on RNA synthesis as compared to DNA synthesis, so that the N-demethyl derivatives showed smaller IC50 ratios on DNA/RNA than their parent compounds.

Animals

Biosynthesis of benastatin A.

The biosynthesis of benastatin A, produced by Streptomyces sp. MI384-DF12, has been studied by feeding experiments with 14C- and 13C-labeled compounds followed by measurement of radioactivity and 13C NMR analysis. The results indicate that benastatin A is derived from two methionine units and fourteen acetate units, condensed in the "head-to-tail" fashion of typical polyketide biosynthesis.

Benz(a)Anthracenes

Dethymicin, a novel immunosuppressant isolated from an Amycolatopsis. Fermentation, isolation, physico-chemical properties and biological activities.

In the course of screening for immunomodulators inhibiting the mixed lymphocyte culture reaction (MLCR), we found a novel immunosuppressant, dethymicin in mycelium of Amycolatopsis mediterranei MI710-51F6. From physico-chemical properties and biological activity it is different from immunosuppressants produced by microorganisms such as cyclosporins, FK506 and rapamycin. It inhibited immune responses in vitro and in vivo, and prolonged skin allograft in rats.

Actinomycetales

Biosynthesis of bellenamine by Streptomyces nashvillensis using stable isotope labeled compounds.

The biosynthesis of bellenamine was studied by feeding 13C and 15N labeled precursors to the synthetic medium culture of Streptomyces nashvillensis MD743-GF4. The high degree of incorporation of D-[1-13C]beta-lysine indicated that it is a direct intermediate, while supplemented L-beta-lysine repressed the production of bellenamine. [2-13C]Glycine was well incorporated into the C-1' of the open-chain aldoaminal structure. All four nitrogens of bellenamine were derived from [15NH4]2SO4 present in the synthetic medium. In the addition of L-lysine and glycine, [15NH4]2SO4 was highly incorporated into CONH. The feeding experiments of 13C labeled acetates suggested that the D-beta-lysine moiety was derived from L-lysine by catalysis of a new 2,3-aminomutase, and L-lysine was biosynthesized from acetates via the TCA cycle and diaminopimelic acid pathway.

Acetates

Preparation of 13C and 15N labeled bellenamine and its degradation products.

A streptomyces metabolite, bellenamine, has been converted into D-beta-lysinamide and cyclized bellenamine in an acidic solution at 75 degrees C. The structure of the new cyclized compound was assigned as (R)-6-(3-aminopropyl)-1,3-diazacyclohexan-4-one by spectral analyses. [1-13C, Amide, 1'-15N2]bellenamine, which has been isolated from the culture by feeding both L-[1-13C]lysine and [15NH4]2SO4 to a synthetic medium, was degraded under acidic condition to obtain the stable isotope labeled D-beta-lysine, D-beta-lysinamide and cyclized bellenamine. These labeled compounds were analyzed by 13C and 15N NMR spectra, and will be used for the biosynthetic study on bellenamine.

Ammonium Sulfate