Novel bibenzyl compound Ae exhibits anti-agiogenic activity in HUVECs in vitro and zebrafish in vivo

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic & Medicinal Chemistry Pub Date : 2024-08-02 DOI:10.1016/j.bmc.2024.117866

Li Guan , Shengjie Zhang , Pengfei Song , Yanxin Xia , Xinle Zheng , Weize Li

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Abstract

The inhibition of angiogenesis has been considered as an attractive method for the discovery of potential anti-cancer drugs. Herein, we report our new synthesized bibenzyl compound Ae had potent anti-angiogenic activity(the lowest effective concentration is to 0.62–1.25 μM) in zebrafish in vivo and showed a concentration-dependent inhibition of inter-segmental blood vessels (ISVs) compared to control. Further, Ae exhibited the obvious inhibitory activity of proliferation, migration, invasion and tube formation in HUVEC cells in vitro. Moreover, qRT-PCR analysis revealed that the anti-angiogenic activity of compound Ae is connected with the ang-2, tek in ANGPT-TEK pathway and the kdr, kdrl signaling axle in VEGF-VEGFR pathway. Molecular docking studies revealed that compound Ae had an interaction with the angiopoietin-2 receptor(TEK) and VEGFR2. Additionally, analysis of the ADMET prediction data indicated that compound Ae possessed favorable physicochemical properties, drug-likeness, and synthetic accessibility. In conclusion, compound Ae had remarkable anti-angiogenic activity and could be served as an candidate for cancer therapy.

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新型双苄化合物 Ae 在体外的 HUVEC 和体内的斑马鱼中表现出抗促老活性。

抑制血管生成一直被认为是发现潜在抗癌药物的一种有吸引力的方法。在此，我们报告了新合成的双苄基化合物 Ae 在斑马鱼体内具有强效的抗血管生成活性（最低有效浓度为 0.62-1.25 μM），与对照组相比，对节段间血管（ISVs）的抑制呈浓度依赖性。此外，Ae 还对体外 HUVEC 细胞的增殖、迁移、侵袭和管形成具有明显的抑制作用。此外，qRT-PCR 分析表明，化合物 Ae 的抗血管生成活性与 ANGPT-TEK 通路中的 ang-2 和 tek 以及 VEGF-VEGFR 通路中的 kdr 和 kdrl 信号轴有关。分子对接研究发现，化合物 Ae 与血管生成素-2 受体（TEK）和血管内皮生长因子受体 2 有相互作用。此外，对 ADMET 预测数据的分析表明，化合物 Ae 具有良好的理化性质、药物相似性和合成可得性。总之，化合物 Ae 具有显著的抗血管生成活性，可作为癌症治疗的候选药物。

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

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.

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