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. 1994 Aug;38(8):1808–1812. doi: 10.1128/aac.38.8.1808

Mechanistic studies and biological activity of bioxalomycin alpha 2, a novel antibiotic produced by Streptomyces viridodiastaticus subsp. "litoralis" LL-31F508.

M P Singh 1, P J Petersen 1, N V Jacobus 1, W M Maiese 1, M Greenstein 1, D A Steinberg 1
PMCID: PMC284640  PMID: 7527199

Abstract

The bioxalomycins, a novel complex of broad-spectrum antibiotics, were isolated from fermentations of Streptomyces viridodiastaticus subsp. "litoralis" LL-31F508. Bioxalomycin alpha 2, the major component of this complex, exhibited antibacterial activity. The MICs ranged from < or = 0.002 to 0.008 micrograms/ml for gram-positive organisms and from 0.50 to 4 micrograms/ml for gram-negative organisms. Bioxalomycin alpha 2 was found to be bactericidal and to inhibit bacterial DNA synthesis preferentially. Bioxalomycin alpha 2 protected mice from a lethal challenge with Staphylococcus aureus Smith. The 50% effective dose of bioxalomycin alpha 2 administered orally was 10 times greater than that when the drug was given subcutaneously or intravenously. These data suggest a stability or bioavailability problem when the compound is administered orally.

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Selected References

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  1. Bull A. T., Goodfellow M., Slater J. H. Biodiversity as a source of innovation in biotechnology. Annu Rev Microbiol. 1992;46:219–252. doi: 10.1146/annurev.mi.46.100192.001251. [DOI] [PubMed] [Google Scholar]
  2. Greenstein M., Speth J. L., Maiese W. M. Mechanism of action of cinodine, a glycocinnamoylspermidine antibiotic. Antimicrob Agents Chemother. 1981 Oct;20(4):425–432. doi: 10.1128/aac.20.4.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hayashi T., Okutomi T., Suzuki S., Okazaki H. Inhibition of nucleic acid biosynthesis in procaryotic and eucaryotic cells by cyanocycline A. J Antibiot (Tokyo) 1983 Sep;36(9):1228–1235. doi: 10.7164/antibiotics.36.1228. [DOI] [PubMed] [Google Scholar]
  4. Hill G. C., Wunz T. P., MacKenzie N. E., Gooley P. R., Remers W. A. Computer simulation of the binding of naphthyridinomycin and cyanocycline A to DNA. J Med Chem. 1991 Jul;34(7):2079–2088. doi: 10.1021/jm00111a024. [DOI] [PubMed] [Google Scholar]
  5. Kluepfel D., Baker H. A., Piattoni G., Sehgal S. N., Sidorowicz A., Singh K., Vézina C. Naphthyridinomycin, a new broad-spectrum antibiotic. J Antibiot (Tokyo) 1975 Jul;28(7):497–502. doi: 10.7164/antibiotics.28.497. [DOI] [PubMed] [Google Scholar]
  6. Omura S. Thom Award Lecture. Trends in the search for bioactive microbial metabolites. J Ind Microbiol. 1992 Sep;10(3-4):135–156. doi: 10.1007/BF01569759. [DOI] [PubMed] [Google Scholar]
  7. Sampson B. A., Misra R., Benson S. A. Identification and characterization of a new gene of Escherichia coli K-12 involved in outer membrane permeability. Genetics. 1989 Jul;122(3):491–501. doi: 10.1093/genetics/122.3.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Silver L. L., Bostian K. A. Discovery and development of new antibiotics: the problem of antibiotic resistance. Antimicrob Agents Chemother. 1993 Mar;37(3):377–383. doi: 10.1128/aac.37.3.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Tomita F., Takahashi K., Shimizu K. DC-52, a novel antitumor antibiotic. 1. Taxonomy, fermentation and biological activity. J Antibiot (Tokyo) 1983 May;36(5):463–467. doi: 10.7164/antibiotics.36.463. [DOI] [PubMed] [Google Scholar]
  10. Walker G. C. Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Microbiol Rev. 1984 Mar;48(1):60–93. doi: 10.1128/mr.48.1.60-93.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Zmijewski M. J., Jr, Miller-Hatch K., Mikolajczak M. The in vitro interaction of naphthyridinomycin with deoxyribonucleic acids. Chem Biol Interact. 1985 Jan;52(3):361–375. doi: 10.1016/0009-2797(85)90030-4. [DOI] [PubMed] [Google Scholar]

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