牛蒡酸A、B、吡咯烷酮生物碱作为M3受体拮抗剂

IF 4.7 2区化学 Q2 CHEMISTRY, PHYSICAL Journal of Molecular Structure Pub Date : 2025-07-05 Epub Date: 2025-03-01 DOI:10.1016/j.molstruc.2025.141920

Yan Li , Bingxiong Yan , Tao Hou , Han Zhou , Xiaomin Xie , Xinmiao Liang , Yunqiu Wu , Lijun Ruan , Caiyun Yao , Zhijun Song , Yanfang Liu

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引用次数: 0

摘要

对水蛭科Pyrrosia calvata (Baker) Ching的化学研究分离出两种先前未被描述的吡咯烷酮生物碱，calvatine A (35), calvatine B(36)，以及12种已知的天然产物。它们的结构解析是基于大量的核磁共振、质谱和ECD数据，并借助于ECD谱的DFT预测。值得注意的是，只有具有r构型的calvatine B对M3受体表现出较强的拮抗活性，IC50值为14.92±6.5 μM。calvatine B（36）与rM3受体对接时，在结合袋内与asn152（3.37）、ALA238（5.46）和ASN507（6.52）三个残基形成氢键，其中ASN507（6.52）被鉴定为M3受体的关键氨基酸。本研究标志着建立一个以实验为基础的网络来描述牛头藤的生物活性成分、靶标活性和传统治疗功能之间的关系的初步努力。

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Calvatine A and B, pyrrolidone alkaloids as M3 receptor antagonists from Pyrrosia calvata

Chemical investigation of Pyrrosia calvata (Baker) Ching (Polypodiaceae) led to the isolation of two previously undescribed pyrrolidone alkaloids, calvatine A (35), calvatine B (36), together with twelve known natural products. Their structure elucidation was based on extensive NMR studies, MS and ECD data, with the essential aid of DFT prediction of ECD spectra. Notably, only calvatine B, bearing an R-configuration, exhibited strong antagonistic activity against the M₃ receptor, with an IC₅₀ value of 14.92 ± 6.5 μM. The docking of calvatine B (36) on the rM₃ receptor exhibited hydrogen bonds with three residues-ASN152(3.37), ALA238(5.46), and ASN507(6.52) within the binding pocket, with ASN507 (6.52) identified as the key amino acid for the M₃ receptor. This study marks the initial effort to construct an experimentally based network delineating the relationships among bioactive components, target activities, and traditional therapeutic functions of P. calvata.

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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.