Biomedical subjects
Publications and source records attributed to H Naganawa.
New ansamycins designated hydroxymycotrienins A and B were isolated from culture broths of Bacillus sp. BMJ958-62F4. The two antibiotics inhibited more strongly the growth of human cervical cancer cell lines of human papilloma virus (HPV) positive than that of HPV negative cell lines. The structures, some biological and biochemical properties are reported.
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Novel antibiotics, pyralomicins 1a approximately 1d, 2a approximately 2c were isolated from the culture broth of Microtetraspora spiralis MI178-34F18. The structures of pyralomicins were determined by various NMR spectral analyses including 1H-15N HMBC and 13C¿1H¿ NOE difference experiments.
The biosynthesis of pyralomicin 1a (1) was studied by feeding of 13C and 15N labeled compounds to the culture of Microtetraspora spiralis MI178-34F18. The result indicated that the benzopyranopyrrole unit of 1 was derived from two units of acetate, one unit of propionate and one unit of proline, and that the cyclitol unit of 1 was derived from glucose metabolites. And 4'-O-CH3 was derived from the S-CH3 group of methionine.
Microbial conversion of beta-rhodomycinone and aklavinone using an aclarubicin-negative Streptomyces galilaeus mutant afforded new anthracycline antibiotics CG21-C and CG1-C which had a rednosyl-2-deoxyfucosyl-rhodosaminyl trisaccharide residue at C-7 of each added aglycone. They were produced only when a prolonged conversion culture took place. Because the usual conversion products containing a cinerulosyl-2-deoxyfucosyl-rhodosaminyl residue were at first accumulated and then decreased during further cultivation, it was evident that they occurred by the modification of terminal cinerulose. The isolation, purification, and structural determination are described, and cytotoxicity in vitro against cultured L1210 cells and the formation mechanism are discussed.
The biochemical basis for the multiple resistance to aminoglycoside antibiotics (AGs) of kasugamycin-producing Streptomyces kasugaensis MB273 was studied. The strain was resistant to a wide range of deoxystreptamine (DOS)-containing AGs as well as astromicin (ASTM) group antibiotics. These AGs strongly inhibited in vitro polyU-directed polyphenylalanine-synthesis using ribosomes from the strain, while they were acetylated and inactivated by the MB273 cell free extract supplemented with acetyl-CoA. It seemed thus likely that the acetyltransferase activity played a critical role for the multiple AG resistance. The acetylation was selective to AGs with 2'-NH2, suggesting the involvement of aminoglycoside 2'-N-acetyltransferase, AAC (2'). Interestingly, the acetylation of istamycin B (ISM-B; an ASTM group AG) resulted in the formation of two different products (1-N-acetyl ISM-B and 2"-N-acetyl ISM-B) at a similar ratio. In this context, an AAC (2') gene cloned as an ISM-B resistance gene from the strain MB273 directed the conversion of ISM-B to only 1-N-acetyl ISM-B. It seemed likely that two types of AACs [AAC(2') and a novel one] were involved in the mechanism of resistance to ASTM group AGs.
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Pyrostatins A and B, new inhibitors of N-acetyl-beta-D-glucosaminidase (GlcNAc-ase), have been purified from the culture broth of Streptomyces sp. SA-3501 isolated from a marine environment. They were purified by chromatography on Dowex 50W, silica gel and Capcell Pak C18 (HPLC) followed treatment with active carbon and then isolated as white powders. The structures of pyrostatins A and B were determined by NMR studies to be 4-hydroxy-2-imino-1-methylpyrrolidine-5-carboxylic acid and 2-imino-1-methylpyrrolidine-5-carboxylic acid, respectively. They were competitive with the substrate, and the inhibition constants (Ki) of pyrostatins A and B were 1.7 x 10(-6) M and 2.0 x 10(-6) M respectively.
Belactins A and B, new inhibitors of serine carboxypeptidase were discovered in the fermentation broth of Saccharopolyspora sp. MK19-42F6. The structures of belactins A and B were determined to be 4-[3-[(2-amino-5-chlorobenzoyl)amino]-1,1-dimethyl-2-oxobutyl]-3- methyl-2-oxetanone and 4-[3-[[2-(beta-glucopyranosylamino)-5-chlorobenzoyl]amino]-1,1- dimethyl-2-oxobutyl]-3-methyl-2-oxetanone respectively by various spectral analyses. Belactins A and B do not inhibit esterase or lipase at 100 micrograms/ml but have more specific inhibitory activities towards carboxypeptidase Y (CP-Y) compared with other beta-lactone-containing inhibitors, such as ebelactones A, B and esterastin.
Novel antimicrobial antibiotics against Pasteurella piscicida, tetrodecamycin (1) and weakly active dihydrotetrodecamycin (2) were isolated from a culture broth of Streptomyces nashvillensis MJ885-mF8. The planar structure of 1 was determined to be 2-acyl-4-ylidene tetronic acid alkyl ether containing decaline ring by various NMR spectral data of 1 and its acetyl derivative (3). The structure of 2 was elucidated by comparison with the spectral data of 1 and confirmed by catalytic reduction of 1 into 2. The X-ray crystallography of 2 showed the relative stereochemistry. Their absolute configurations were determined by using modified Mosher's method.
A new structural class of antibiotics, azicemicins A (1) and B (2) were isolated from the culture broth of Amycolatopsis sp. MJ126-NF4. Their structures were elucidated from their physico-chemical properties, various NMR experiments and chemical transformations and were shown to be 3-(1-methyl-2-aziridinyl)- and 3-(2-aziridinyl)-3,4-dihydro-3,7,8,10,12b-pentahydroxy-9,12-dimeth oxy-benz [a]anthracene-1,6(2H,5H)-dione, respectively.
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New triene-ansamycins designated thiazinotrienomycins A, B, C, D and E were isolated from culture broth of Streptomyces sp. MJ672-m3 for their activities against cervical cancer cell lines. The structures and some biological and biochemical properties of the antibiotics were determined.
In the course of our screening for inhibitors of abl oncogene function, a culture filtrate of Streptomyces aculeolatus, induced normal flat morphology in v-abl-expressing NIH3T3 cells. The active substance was isolated through ethyl acetate extraction, silica gel column chromatography, and reverse-phase HPLC. Mass and NMR spectroscopy including HMBC revealed that it had a novel naphthoquinone structure with a monoterpene, and we named it "naphthablin". Naphthablin inhibited Abl-induced morphological transformation in v-ablts-NIH3T3 cells at around 30 micrograms/ml, and specifically inhibited RNA synthesis.