Synthesis and Antiviral Activity of 21β-Acetyl-20β,28-Epoxy-18α,19βH-Ursane Derivatives Against Influenza H1N1 and SARS-Cov-2 Spike Pseudovirus

IF 0.8 4区化学 Q4 CHEMISTRY, MEDICINAL Chemistry of Natural Compounds Pub Date : 2024-03-26 DOI:10.1007/s10600-024-04302-w

E. F. Khusnutdinova, Z. I. Galimova, A. V. Petrova, E. V. Tretyakova, I. E. Smirnova, A. V. Slita, S. V. Fedij, V. V. Zarubaev, S. Xiao, X. Ma, D. Zhou, T. V. Rybalova, D. N. Polovyanenko, O. B. Kazakova

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Abstract

Allobetulin derivatives with rearranged E-ring exhibit important pharmacological properties against various viral pathogens. Basing on 3β-acetoxy-21β-acetyl-20β,28-epoxy-18α,19βH-ursane triterpenoid, obtained from allobetulin in one stage, a series of new derivatives have been synthesized and their antiviral activity against both influenza virus A (H1N1) and SARS-CoV-2 pseudovirus was evaluated. Among them, 2,3-indolo-allobetulone N-propargyl derivatives were the most efficacious against influenza virus with low toxicity (CC₅₀ × 300 μM) and IC₅₀ values of 7.04 to 3.5 μM and high selectivity indexes (SI 43 and 86). Compared with amodiaquine, a derivative with 3-pyridinylidene fragment 12 showed a weak antiviral activity against SARS-CoV-2 pseudovirus with an inhibition rate of 57.3% at a concentration of 20 μM. Further optimization to increase the cellular antiviral activity seems to be necessary to develop this series of triterpenoids as antiviral agents.

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21β-Acetyl-20β,28-Epoxy-18α,19βH-Ursane 衍生物的合成及其对 H1N1 流感和 SARS-Cov-2 Spike 伪病毒的抗病毒活性

具有重新排列 E 环的阿洛贝杜林衍生物对多种病毒病原体具有重要的药理特性。以从阿洛贝杜林中一步获得的 3β-乙酰氧基-21β-乙酰基-20β,28-环氧-18α,19βH-乌苏烷三萜为基础，合成了一系列新的衍生物，并评估了它们对甲型 H1N1 流感病毒和 SARS-CoV-2 伪病毒的抗病毒活性。其中，2,3-吲哚-阿洛贝酮 N-丙炔基衍生物对流感病毒最有效，毒性低（CC50 × 300 μM），IC50 值为 7.04 至 3.5 μM，选择性指数高（SI 43 和 86）。与阿莫地喹相比，具有 3-吡啶亚基片段 12 的衍生物对 SARS-CoV-2 伪病毒的抗病毒活性较弱，在 20 μM 的浓度下抑制率为 57.3%。要将这一系列三萜类化合物开发成抗病毒药物，似乎有必要进一步优化以提高其细胞抗病毒活性。

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来源期刊

Chemistry of Natural Compounds 化学-有机化学

CiteScore

1.40

自引率

25.00%

发文量

265

审稿时长

7.8 months

期刊介绍： Chemistry of Natural Compounds publishes reviews and general articles about the structure of different classes of natural compounds, the chemical characteristics of botanical families, genus, and species, to establish the comparative laws and connection between physiological activity and the structure of substances.