Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-Ku, Tokyo, 142-8501, Japan.
Research Center for Infectious Disease Control, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
J Nat Med. 2024 Jan;78(1):68-77. doi: 10.1007/s11418-023-01746-2. Epub 2023 Sep 10.
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 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.
陶瓷宁是从马来西亚的麻疯树（Meliaceae）树皮中分离得到的一系列柠檬苦素，已知具有多种生物活性。从麻疯树的树皮中分离得到了 6 个新的柠檬苦素，陶瓷宁 U-Z（1-6），它们具有一个环戊酮[α]菲环系统，在 C-17 处具有一个β-呋喃环。基于 1D 和 2D NMR 分析确定了它们的结构，并通过 CD 光谱研究了它们的绝对构型。陶瓷宁 W（3）对恶性疟原虫 3D7 株表现出很强的抗疟活性，IC 值为 1.2µM。此外，还研究了陶瓷宁的结构-抗疟活性关系（SAR），以确定可能增强活性的取代模式。似乎 B 环和 B 环和 C 环附近的官能团对陶瓷宁的抗疟活性至关重要。特别是，在 C-7 和 C-12 处具有赤道取向的大酯取代基极大地提高了抗疟活性。
