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Structures and biological activities of novel 4’-acetylated analogs of chrysomycins A and B

  • The Journal of Antibiotics volume 70, pages 10781082 (2017)
  • doi:10.1038/ja.2017.99
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Abstract

Two new 4’-acetylated analogs of chrysomycin were discovered during the screening for antitumor agents from the metabolites of actinomycetes. Their structures and physicochemical properties were determined by standard spectrometric analyses. Their cytotoxicities and antimicrobial activities were evaluated against a panel of cancer cell lines and microbes. While acetylation reinforced the cytotoxicity of chrysomycin B, it weakened the activity of chrysomycin A. Chrysomycin A and its acetylated analog showed high cytotoxicity toward most of the cancer cells with IC50s less than 10 ng ml−1. The 4’-acetyl-chrysomycin A was predominantly observed in nuclei at concentrations where the autofluorescence was observable. Chrysomycins were effective toward Gram-positive bacteria. The 4’-acetylated-chrysomycin A and B had MICs of 0.5–2 μg ml−1 and 2 to greater than 64 μg ml−1, respectively, toward Gram-positive bacteria including MRSA and VRE.

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References

  1. 1.

    et al. The chemistry of the antibiotics chrysomycin A and B. Antitumor activity of chrysomycin A. J. Antibiot. 35, 1194–1201 (1982).

  2. 2.

    , , & Gilvocarcins, new antitumor antibiotics. 2. Structural elucidation. J. Antibiot. 34, 271–275 (1981).

  3. 3.

    , , & The structure of ravidomycin. Can. J. Chem 59, 3018–3020 (1981).

  4. 4.

    , & On the structure, chemistry, and C-13 nuclear magnetic-resonance of ravidomycin. Can. J. Chem. 61, 323–327 (1983).

  5. 5.

    et al. Plasticity in gilvocarcin-type C-glycoside pathways: discovery and antitumoral evaluation of polycarcin V from Streptomyces polyformus. Org. Biomol. Chem. 6, 3601–3605 (2008).

  6. 6.

    et al. Antitumor activity of chrysomycins M and V. J. Antibiot. 42, 1446–1448 (1989).

  7. 7.

    et al. Gilvocarcins, new antitumor antibiotics. 1. Taxonomy, fermentation, isolation and biological activities. J. Antibiot. 34, 266–270 (1981).

  8. 8.

    , , & Gilvocarcins, new antitumor antibiotics. 3. Antitumor activity. J. Antibiot. 34, 701–707 (1981).

  9. 9.

    & Biochemical characterisation of elsamicin and other coumarin-related antitumour agents as potent inhibitors of human topoisomerase II. Eur. J. Cancer 29A, 1985–1991 (1993).

  10. 10.

    & Histone H3 and heat shock protein GRP78 are selectively cross-linked to DNA by photoactivated gilvocarcin V in human fibroblasts. Cancer Res. 60, 3921–3926 (2000).

  11. 11.

    et al. Phase II study of elsamitrucin in non-small cell lung cancer. Invest. New Drugs 12, 315–317 (1994).

  12. 12.

    et al. Phase II study of elsamitrucin (BMY-28090) for the treatment of patients with refractory/relapsed non-Hodgkin's lymphoma. Invest. New Drugs 14, 213–217 (1996).

  13. 13.

    , & Chrysomycin: a new antibiotic substance for bacterial viruses. J. Bacteriol. 69, 280–283 (1955).

  14. 14.

    et al. Formation of new antibiotic, virenomycin, by a culture of Streptomyces virens sp. nev. Antibiotiki. 22, 963–967 (1977).

  15. 15.

    et al. Physico-chemical characteristics of the new antitumor antibiotic virenomycin. Antibiotiki. 22, 967–970 (1977).

  16. 16.

    et al. Separation and characteristics of the components of the antibiotic virenomycin. Antibiotiki. 27, 507–511 (1982).

  17. 17.

    et al. Structure of the antibiotic virenomycin. Antibiotiki. 29, 884–892 (1984).

  18. 18.

    et al. Chrysomycins A-C, antileukemic naphthocoumarins from Streptomyces sporoverrucosus. RSC Adv. 3, 21046–21053 (2013).

  19. 19.

    & Mitochondrial DNA is a direct target of anti-cancer anthracycline drugs. Biochem. Biophys. Res. Commun. 378, 450–455 (2009).

  20. 20.

    , , & Studies on the mechanism of actin of gilvocarcin V and chrysomycin A. J. Antibiot. 35, 545–548 (1982).

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Acknowledgements

This work was supported by the Japan Society for the Promotion of Science (23701108, 15K08013 and 26450107). We acknowledge colleagues at the Institute of Microbial Chemistry for their support of this study and for helpful discussions.

Author information

Affiliations

  1. Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan

    • Shun-ichi Wada
    • , Ryuichi Sawa
    • , Fumiki Iwanami
    • , Miho Nagayoshi
    • , Yumiko Kubota
    • , Kiyoko Iijima
    • , Chigusa Hayashi
    • , Yuko Shibuya
    • , Masaki Hatano
    • , Masayuki Igarashi
    •  & Manabu Kawada

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to Shun-ichi Wada.

Supplementary information

Supplementary Information accompanies the paper on The Journal of Antibiotics website (http://www.nature.com/ja)