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

• Published in: Journal of natural medicines Vol. 78; no. 1; pp. 68 - 77
• Main Authors: Nugroho, Alfarius Eko, Komuro, Tomoyuki, Kawaguchi, Takuya, Shindo, Yusuke, Wong, Chin Piow, Hirasawa, Yusuke, Kaneda, Toshio, Tougan, Takahiro, Horii, Toshihiro, Hadi, A. Hamid A., Morita, Hiroshi
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.01.2024; Springer Nature B.V
• Subjects: Antimalarial activity; antimalarials; Antimalarials - pharmacology; Antiparasitic agents; bioactive properties; Biological activity; Biomedical and Life Sciences; Biomedicine; Chisocheton; Complementary & Alternative Medicine; Limonins - chemistry; limonoids; Magnetic Resonance Spectroscopy; Malaria; Medicinal Chemistry; Meliaceae - chemistry; Molecular Structure; Original Paper; Pharmacology/Toxicology; Pharmacy; Phenanthrene; phenanthrenes; Plant Sciences; Plasmodium falciparum; Spectroscopy; Structure-Activity Relationship; Antimalarial activity; Structure–antimalarial activity relationship; Ceramicines U–Z; Meliaceae; Limonoids; Chisocheton ceramicus
• ISSN: 1340-3443; 1861-0293; 1861-0293
• DOI: 10.1007/s11418-023-01746-2

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 IC 50 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. Graphical Abstract