Identification of topoisomerases as molecular targets of cytosporolide C and its analog

Keisuke Otake, Kana Yamada, Kazuki Miura, Yukiko Sasazawa, So Miyazaki, Yuki Niwa, Akihiro Ogura, Ken ichi Takao, Siro Simizu

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Cytosporolide (Cytos) A–C, isolated from the fungus Cytospora sp., have anti-microbial activity, but their molecular targets in mammalian cells are unknown. We have previously reported the total synthesis of Cytos A by biomimetic hetero-Diels-Alder reaction. In this study, to examine the novel bioactivity of Cytos, we synthesized Cytos C and measured cell growth-inhibiting activities of 7 compounds, including Cytos A and C, in several human cancer cell lines. Among these compounds, Cytos C and tetradeoxycytosporolide A (TD-Cytos A), a model compound for the synthesis of Cytos A, had anti-proliferative effects on cancer cells, and TD-Cytos A exhibited stronger activity than Cytos C. In vitro topoisomerase-mediated DNA relaxing experiments showed that TD-Cytos A inhibited the activities of topoisomerase I and II, whereas Cytos C targeted only topoisomerase I. These data suggest that the anti-proliferative activities of Cytos correlate with the inhibition of topoisomerases and implicated TD-Cytos A as a novel anti-cancer drug that suppresses the activities of topoisomerase I and II.

Original languageEnglish
Pages (from-to)3334-3338
Number of pages5
JournalBioorganic and Medicinal Chemistry
Issue number15
Publication statusPublished - 2019 Aug 1


  • Anti-cancer drug
  • Cytosporolide
  • Natural product
  • Topoisomerase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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