Acronynoids A-G, novel prenylated acetophenone-based meroterpenoids with angiogenesis inhibitory activities from Acronychia pedunculata

IF 4.7 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2025-06-01 Epub Date: 2025-03-15 DOI:10.1016/j.bioorg.2025.108376

Zhen-Zhen Yang , Mu Chen , Xin-Yi Gao , Liang Long , Hai-Wang Yang , Yan Wu , Jun-Cheng Su , Yang Chen , Xue-Ping Lei , Ji-Hong Gu

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Abstract

Seven novel prenylated acetophenone-based meroterpenoids with new carbon skeletons, acronynoids A-G (1-7), were isolated from Acronychia pedunculata. These compounds represent the first examples of bis-prenylated acetophenone-sesquiterpenoid adducts, in which 1 featured a unique 6/6/6/9/4 fused pentacyclic ring system. Their structures with absolute configurations were established by extensive spectroscopic analyses and quantum-chemical calculations. A plausible biogenetic pathway of these isolates was proposed. Moreover, all the isolates were evaluated for their angiogenesis inhibitory activities against human microvascular endothelial cells (HMEC-1). Compound 2, as the best representative, not only inhibited the tube formation, migration, and invasion of endothelial cells, but also effectively reduced angiogenesis in zebrafish model. Further research revealed that 2 suppressed the expression of Gli1, a key regulator of angiogenesis.

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首字母缩略词A-G：具有抑制血管生成活性的新戊基苯乙酮类缩萜类化合物

从长柄首字母缩略词中分离到7个具有新碳骨架的苯乙酮基戊烯基新萜类化合物，首字母缩略词A-G（1-7）。这些化合物是双戊烯基化苯乙酮倍半萜类加合物的第一个例子，其中1具有独特的6/6/6/9/4融合五环体系。它们具有绝对构型的结构是通过广泛的光谱分析和量子化学计算确定的。提出了一种合理的生物遗传途径。此外，所有分离物对人微血管内皮细胞（HMEC-1）的血管生成抑制活性进行了评估。以化合物2为最佳代表，在斑马鱼模型中，化合物2不仅能抑制内皮细胞的管状形成、迁移和侵袭，还能有效减少血管生成。进一步的研究发现，2抑制Gli1的表达，Gli1是血管生成的关键调节因子。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.