Targeted Isolation of Antiviral Labdane Diterpenes from the Bark of Neo-uvaria foetida (Annonaceae) using LC-MS/MS-Based Molecular Networking.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2024-08-23 Epub Date: 2024-07-19 DOI:10.1021/acs.jnatprod.4c00342

S Yaallini Sukumaran, Charline Herrscher, Nurulfazlina Edayah Rasol, Muhamad Aqmal Othman, Sook Yee Liew, Nor Hadiani Ismail, Karin Séron, Marc Litaudon, Khalijah Awang, Chaker El Kalamouni, Cécile Apel, Azeana Zahari

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Abstract

In the search of new inhibitors for human coronavirus (HCoV), we screened extracts of endemic Annonaceae plants on an assay using a cellular model of Huh-7 cells infected with the human alphacoronavirus HCoV-229E. The EtOAc bark extract of the rare Southeast Asian plant Neo-uvaria foetida exhibited inhibition of HCoV-229E and SARS-CoV-2 viruses with IC₅₀ values of 3.8 and 7.8 μg/mL, respectively. Using LC-MS/MS and molecular networking analysis guided isolation, we discovered two new labdane-type diterpenoids, 8-epi-acuminolide (1) and foetidalabdane A (4), and three known labdane diterpenoids, acuminolide (2), 17-O-acetylacuminolide (3), and spiroacuminolide (5). A new norlabdane diterpene, 16-foetinorlabdoic acid (6), was also isolated and identified. Excluding compounds 5 and 6, all other metabolites were active against the virus HCoV-229E. Terpenoids 1 and 4 presented antiviral activity against SARS-CoV-2 with IC₅₀ values of 63.3 and 93.5 μM, respectively, indicating lower potency. Additionally, virological assays demonstrated that compounds 1, 2, and 3 exert antiviral effects against Zika virus by specifically interfering with the late stage of its infectious cycle with IC₅₀ values of 76.0, 31.9, and 14.9 μM, respectively.

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利用基于 LC-MS/MS 的分子网络，从新桉树树皮中定向分离出抗病毒的拉巴旦二萜。

为了寻找新的人类冠状病毒（HCoV）抑制剂，我们利用感染了人类α-冠状病毒 HCoV-229E 的 Huh-7 细胞模型，对当地特有的芒萁科植物的提取物进行了筛选。东南亚稀有植物Neouvaria foetida的乙酸乙酯树皮提取物对HCoV-229E和SARS-CoV-2病毒有抑制作用，IC50值分别为3.8和7.8微克/毫升。利用 LC-MS/MS 和分子网络分析指导分离，我们发现了两种新的拉布丹类二萜，即 8-epi-acuminolide (1) 和 foetidalabdane A (4)，以及三种已知的拉布丹类二萜，即 acuminolide (2)、17-O-乙酰基 acuminolide (3) 和 spiroacuminolide (5)。此外，还分离并鉴定出了一种新的去甲唇形二萜--16-foetinorlabdoic acid（6）。除化合物 5 和 6 外，所有其他代谢物都对 HCoV-229E 病毒具有活性。萜类化合物 1 和 4 对 SARS-CoV-2 具有抗病毒活性，其 IC50 值分别为 63.3 和 93.5 μM，表明其效力较低。此外，病毒学实验表明，化合物 1、2 和 3 通过特异性干扰寨卡病毒感染周期的后期阶段，对其产生抗病毒作用，其 IC50 值分别为 76.0、31.9 和 14.9 μM。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.