从 Casearia graveolens 中发现靶向 VEGFR-2 的抗肿瘤二萜类化合物，从而抑制血管生成

IF 4 2区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Journal of Natural Medicines Pub Date : 2024-09-01 DOI:10.1016/S1875-5364(24)60566-2

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引用次数: 0

摘要

从Casearia graveolens的小枝中分离出了八种新型萜类化合物（1-8）。通过全面的核磁共振（NMR）、高分辨率电喷雾质谱（HR-ESI-MS）和电子圆二色性（ECD）分析，阐明了它们的结构。除了结构测定外，还进行了表面等离子体共振（SPR）测定以研究分子相互作用，结果表明化合物 8 对血管内皮生长因子受体 2（VEGFR2）具有很高的亲和力，而血管内皮生长因子受体 2 是肿瘤血管生成的关键调节因子。随后的体内实验表明，化合物 8 能有效抑制血管生成，并在斑马鱼异种移植模型中通过抑制肿瘤增殖和转移而显示出显著的抗肿瘤活性。这些研究结果表明，化合物 8 有望成为以 VEGFR-2 为靶点阻碍肿瘤血管生成的抗癌先导化合物。

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Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis

Eight novel clerodane diterpenoids (1−8) were isolated from the twigs of Casearia graveolens. Their structures were elucidated through comprehensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and electronic circular dichroism (ECD) analyses. In addition to structural determination, surface plasmon resonance (SPR) assays were conducted to investigate molecular interactions, revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis. Subsequent in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models. These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.

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来源期刊

Chinese Journal of Natural Medicines INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY

CiteScore

7.50

自引率

4.30%

发文量

2235

期刊介绍： The Chinese Journal of Natural Medicines (CJNM), founded and sponsored in May 2003 by China Pharmaceutical University and the Chinese Pharmaceutical Association, is devoted to communication among pharmaceutical and medical scientists interested in the advancement of Traditional Chinese Medicines (TCM). CJNM publishes articles relating to a broad spectrum of bioactive natural products, leading compounds and medicines derived from Traditional Chinese Medicines (TCM). Topics covered by the journal are: Resources of Traditional Chinese Medicines; Interaction and complexity of prescription; Natural Products Chemistry (including structure modification, semi-and total synthesis, bio-transformation); Pharmacology of natural products and prescription (including pharmacokinetics and toxicology); Pharmaceutics and Analytical Methods of natural products.