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

Nugroho AE 1 , Komuro T 1 , Kawaguchi T 1 , Shindo Y 1 , Wong CP 1 , Hirasawa Y 2 Show all authors , Kaneda T 1 , Tougan T 3 , Horii T 4 , Hadi AHA 5 , Morita H 6

Affiliations 

  • 1 Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo, 142-8501, Japan
  • 2 Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo, 142-8501, Japan. y-hirasawa@hoshi.ac.jp
  • 3 Research Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
  • 4 Department of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
  • 5 Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia
  • 6 Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo, 142-8501, Japan. moritah@hoshi.ac.jp
J Nat Med, 2024 Jan;78(1):68-77.
PMID: 37690111 DOI: 10.1007/s11418-023-01746-2

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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