Triterpene derivatives from Diospyros anisandra S. F. Blake against influenza A (H1N1) virus: In vitro and in silico assays

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Molecular Structure Pub Date : 2025-10-05 DOI:10.1016/j.molstruc.2025.144267

Mari Toña Juárez-Méndez , Gloria Jiménez-Alcalá , Rocío Borges-Argáez , Ivan Chan-Zapata , Guadalupe Ayora-Talavera , Norma A. Caballero , Francisco J. Melendez , María Eugenia Castro

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引用次数: 0

Abstract

Diospyros anisandra S. F. Blake (Ebenaceae) is a quasi-endemic species of the Yucatan Peninsula, Mexico, that has shown activity against influenza A viruses. D. anisandra is rich in quinones and terpenes, with over 20 compounds of this type identified in extracts of the species. However, the cytotoxic and antiviral potential of uvaol, taraxerol, and taraxerone have not yet been investigated. This study aimed to determine the cytotoxic and the potential antiviral effects of five triterpenes (taraxerol, taraxerone, uvaol, betulin, and betulinic acid) identified in D. anisandra, as well as three triterpene-rich fractions (D567A7, 3F23, and 4R34). Cytotoxicity was evaluated using Madin-Darby canine kidney (MDCK) cells. To assess the antiviral activity, a cytopathic effect (CPE) reduction assay was performed using the influenza virus A/Yucatan/2370/09 (H1N1) pdm. Betulinic acid was the most cytotoxic compound, with a mean cytotoxic concentration (CC₅₀) of 28.64 μM. The other triterpenes and fractions demonstrated no cytotoxicity. All the triterpene compounds, fraction D567A7 (50 μg/mL), and fraction 4R34 (100 μg/mL) showed a CPE reduction below to 40 %. In silico study was conducted using crystallized viral proteins. All triterpenoids interacted with the key amino acid residues in the active site, albeit to a lesser extent than approved antivirals. This is the first report to evaluate uvaol, taraxerol, and taraxerone in viral assays and molecular docking calculations, contributing to the pharmacological and phytochemical knowledge of D. anisandra and its natural products.

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抗甲型H1N1流感病毒三萜衍生物的体外和计算机分析

Diospyros anisandra s.f. Blake （Ebenaceae）是墨西哥尤卡坦半岛的一种准地方性物种，已显示出对甲型流感病毒的活性。八味子含有丰富的醌类和萜烯，在该物种的提取物中鉴定出超过20种这类化合物。然而，uvaol， taraxerol和taraxerone的细胞毒性和抗病毒潜力尚未被研究。本研究旨在确定五种三萜（taraxerol, taraxerone, uvaol, betulin, and betulinic acid）以及三种富含三萜的部位（D567A7, 3F23, 4R34）的细胞毒性和潜在抗病毒作用。用Madin-Darby犬肾（MDCK）细胞评价细胞毒性。为了评估抗病毒活性，使用流感病毒a /Yucatan/2370/09 (H1N1) pdm进行细胞病变效应（CPE）降低试验。白桦酸是最具细胞毒性的化合物，其平均细胞毒性浓度（CC50）为28.64 μM。其他三萜及其组分无细胞毒性。所有三萜化合物，D567A7 （50 μg/mL）和4R34 （100 μg/mL）的CPE均降低40%以下。用结晶病毒蛋白进行计算机研究。所有的三萜都与活性位点的关键氨基酸残基相互作用，尽管作用程度低于已批准的抗病毒药物。这是第一个在病毒分析和分子对接计算中评估uvaol， taraxerol和taraxerone的报告，有助于了解茴芹及其天然产物的药理学和植物化学知识。

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 Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.