6-Deoxy-8-O-methylrabelomycin and 8-O-methylrabelomycin from a Streptomyces species.
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Biomedical subjects
Publications and source records attributed to K Isshiki.
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Terpentecin at a concentration of 0.78 microgram/ml decreased the number of viable cells of Escherichia coli NIHJ to less than one thousandth the starting number in an hour when added to an exponentially growing culture in a nutrient broth. During this time, the turbidity of the cell suspension kept increasing as fast as the control. Microscopic inspection of the cells exposed to terpentecin under these conditions revealed that the cells were elongated. Terpentecin at a concentration of 6.25 micrograms/ml inhibited incorporation of [14C]thymidine into the acid-insoluble material of cells of E. coli NIHJ by 70% in 30 minutes in contrast to little or no inhibition of the incorporation of [14C]uridine or [14C]leucine. Under similar conditions, terpentecin did not inhibit either membrane transport (uptake) of [14C]thymidine into the cells or the metabolic conversion of the precursor into various cellular acid-soluble components. Terpentecin at a higher concentration (70 micrograms/ml) inhibited by 40% in 30 minutes the incorporation of [methyl-3H]thymidine triphosphate into the DNA fraction of toluene-treated cells of E. coli JE6296 (pol A-). Terpentecin showed stronger antibacterial activities against Bacillus subtilis M45T (rec-) and E. coli BE1121 (rec A-) than against their corresponding wild type strains. However, terpentecin showed no mutagenicity by the Ames test with Salmonella typhimurium strains TA100, TA98, TA92, TA1538, TA1537 and TA1535, and with E. coli WP2 (uvr A). Terpentecin at a lower concentration (0.07 micrograms/ml) inhibited growth in vitro of mouse leukemia L1210 cells by 50%. With the mammalian cells again the incorporation of [14C]thymidine into the acid-insoluble cell material was inhibited more strongly than incorporation of [14C]uridine and [14C]leucine. There was no sign of mutagenicity by the micronucleus test using mice.
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Biosynthetic studies on napyradiomycins were carried out based on the incorporation of [2-13C]acetate and [1,2-13C]acetate. The alignment of acetate units suggested that the B and C rings of napyradiomycins are derived from a pentaketide, while ring A and the side chain may be synthesized from mevalonate.
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Structures of novel antibiotics, napyradiomycins A, B1, B2, B3, C1 and C2 were determined. By X-ray crystallography, napyradiomycin B2 was determined to be (3R,10aR)-3-chloro-10a-[[(1R,3S)-3-chloro-2, 2-dimethyl-6-methylenecyclohexyl]methyl]-3,10a-dihydro-6,8-dihydro xy-2, 2-dimethyl-2H-naphtho[2,3-b]pyran-5,10-dione. The structures of other napyradiomycins were elucidated by NMR studies. Napyradiomycins C1 and C2 have unique structures which contain 14-membered ring cyclized by carbon-carbon bond.
A new antitumor antibiotic, terpentecin was isolated from the culture broth of strain MF730-N6. Strain MF730-N6, isolated from soil, was found to belong to the genus Kitasatosporia. The antibiotic was extracted with chloroform, purified by column chromatography using silica gel and Diaion HP-20 successively, and finally purified by high performance reverse-phase thin layer chromatography. The molecular formula of terpentecin was determined to be C20H28O6 (molecular weight, 364). The antibiotic inhibited the growth of Gram-positive and Gram-negative bacteria, and prolonged the survival period of mice bearing leukemia L-1210, P388 and Ehrlich ascites carcinoma.
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