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Ceramicines U–Z from Chisocheton ceramicus and structure–antimalarial activity relationship study

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Abstract

Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U–Z (1–6), with a cyclopentanone[α]phenanthrene ring system with a β-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their structures were determined on the basis of the 1D and 2D NMR analyses, and their absolute configurations were investigated by CD spectroscopy. Ceramicine W (3) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 1.2 µM. In addition, the structure–antimalarial activity relationship (SAR) of the ceramicines was investigated to identify substituent patterns that may enhance activity. It appears that ring B and the functional groups in the vicinity of rings B and C are critical for the antimalarial activity of the ceramicines. In particular, bulky ester substituents with equatorial orientation at C-7 and C-12 greatly increase the antimalarial activity.

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Acknowledgements

The authors would like to thank Prof. Masatsugu Kimura (Osaka City University, Osaka, Japan) for the kind gift of the 3D7 strain, Mr. Yuji Toya and Dr. Kinya Uchihashi (Sysmex) for the setting of the XN-30 analyzer, and Ms. Toshie Ishisaka and Ms. Sawako Itagaki for their technical assistance. This work was partly supported by JSPS KAKENHI (JP 19K07152 and JP 22K06671 to MH), (JP 16K08309 to AEN), and (JP 22K06685 to YH), Japan.

Funding

This work was partly supported by JSPS KAKENHI (JP 19K07152 and JP 22K06671 to MH), (JP 16K08309 to AEN), and (JP 22K06685 to YH), Japan.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo, 142-8501, Japan

    Alfarius Eko Nugroho, Tomoyuki Komuro, Takuya Kawaguchi, Yusuke Shindo, Chin Piow Wong, Yusuke Hirasawa, Toshio Kaneda & Hiroshi Morita

  2. Research Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Takahiro Tougan

  3. Department of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Toshihiro Horii

  4. Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

    A. Hamid A. Hadi

Authors
  1. Alfarius Eko Nugroho
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  2. Tomoyuki Komuro
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  3. Takuya Kawaguchi
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  4. Yusuke Shindo
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  5. Chin Piow Wong
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  6. Yusuke Hirasawa
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  7. Toshio Kaneda
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  8. Takahiro Tougan
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  9. Toshihiro Horii
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  10. A. Hamid A. Hadi
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  11. Hiroshi Morita
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Contributions

AEN, TK, TK, Y, TT, TH, AHAH, and HM conceived and designed the experiments; AEN, CPW, YH, TK, and HM wrote the paper.

Corresponding authors

Correspondence to Yusuke Hirasawa or Hiroshi Morita.

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Nugroho, A.E., Komuro, T., Kawaguchi, T. et al. Ceramicines U–Z from Chisocheton ceramicus and structure–antimalarial activity relationship study. J Nat Med 78, 68–77 (2024). https://doi.org/10.1007/s11418-023-01746-2

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  • DOI: https://doi.org/10.1007/s11418-023-01746-2

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