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

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2023-09-10 DOI:10.1007/s11418-023-01746-2

Alfarius Eko Nugroho, Tomoyuki Komuro, Takuya Kawaguchi, Yusuke Shindo, Chin Piow Wong, Yusuke Hirasawa, Toshio Kaneda, Takahiro Tougan, Toshihiro Horii, A. Hamid A. Hadi, Hiroshi Morita

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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.

Graphical Abstract

Abstract Image

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来自 Chisocheton ceramicus 的陶瓷碱 U-Z 以及结构-抗疟活性关系研究。

Ceramicines 是一系列从马来西亚 Chisocheton ceramicus（木犀科）树皮中分离出来的柠檬醛类化合物，具有多种生物活性。从 Ceramicus 树皮中分离出了六种新的柠檬醛类化合物，即 ceramicines U-Z（1-6），其环戊酮[α]菲环系统在 C-17 处有一个 β-呋喃环。根据一维和二维核磁共振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。陶瓷碱 W (3) 对恶性疟原虫 3D7 株具有很强的抗疟活性，IC50 值为 1.2 µM。此外，研究人员还对陶瓷碱的结构-抗疟活性关系（SAR）进行了研究，以确定可提高活性的取代基模式。看来，环 B 以及环 B 和环 C 附近的官能团对陶瓷碱的抗疟活性至关重要。特别是在 C-7 和 C-12 处具有赤道取向的笨重酯取代基大大提高了抗疟活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.