Original Article

Biological activity of intervenolin analogs with a phenyl substituent

  • The Journal of Antibiotics volume 71, pages 8690 (2018)
  • doi:10.1038/ja.2017.123
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Abstract

Intervenolin analogs with a phenyl substituent at the 2- or 3-position were synthesized. The compounds (311) showed weak or no inhibitory activity toward the growth of MKN-74 gastric adenocarcinoma cells, even in the presence or absence of the corresponding Hs738 stromal cells, whereas 2-substituted analogs exhibited selective anti-Helicobacter pylori activity. Introduction of a pendant side chain on the nitrogen alleviated their acute toxicity in mice. The 2-phenyl-substituted analogs are reasonable structural templates for structure–activity relationship studies toward the development of anti-H. pylori agents that do not affect human cells.

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Acknowledgements

MK, HA and TW are grateful to the Japan Agency for Medical Research and development (AMED) (the Project for Cancer Research And Therapeutic Evolution (P-CREATE)) for financial support. We thank Dr Ryuichi Sawa, Ms Yumiko Kubota, Dr Kiyoko Iijima and Ms Yuko Takahashi (BIKAKEN) for spectroscopic analysis.

Author information

Affiliations

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

    • Hikaru Abe
    • , Manabu Kawada
    • , Masayuki Igarashi
    • , Chigusa Hayashi
    • , Chiharu Sakashita
    • , Takumi Watanabe
    •  & Masakatsu Shibasaki
  2. Institute of Microbial Chemistry (BIKAKEN), Shizuoka, Japan

    • Manabu Kawada
    •  & Shun-ichi Ohba

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Competing interests

The authors declare no conflict of interest.

Corresponding authors

Correspondence to Takumi Watanabe or Masakatsu Shibasaki.

Supplementary information

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