Abuzenadah Adel M, Al-Sayes Fatin, Mahafujul Alam Syed Sahajada, Hoque Mehboob, Karim Sajjad, Hussain Ibtessam M R, Tabrez Shams
Department of Medical Laboratory Science, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Evid Based Complement Alternat Med. 2022 Feb 14;2022:6224666. doi: 10.1155/2022/6224666. eCollection 2022.
Angiogenesis plays a critical role in tumorigenesis as it provides the necessary blood supply to the newly grown solid tumor. It helps maintain the tumor microenvironment, promotes tumor development, progression, and metastasis. The vascular epithelial growth factor (VEGF), interacting with the tyrosine kinase receptor VEGFR-2 on endothelial cells, exerts its proangiogenic activity. Hence, targeting the VEGFR-2 signaling is considered a promising strategy to inhibit angiogenesis and thus cancer treatment. This study aims to identify the bioactive compounds derived from the medicinal herb that effectively binds with VEGFR-2. The bioactive compounds of were first screened for their physicochemical properties using the DataWarrior program (version 5.5.0). Finally, 17 compounds that obeyed Lipinski's rule of five and showed good drug-likeness were selected for molecular docking studies. Molecular docking results showed that the ligands ajmalicidine, 1, 2-dihydrovomilenine, rauwolscine, yohimbine, ajmaline, and papaverine interact strongly with the target VEGFR-2 receptor. Hydrogen bonds and hydrophobic interactions stabilized the interactions of these compounds with VEGFR-2. These compounds showed favourable drug-like properties and possess no significant toxicity. Therefore, the findings of this study indicate that the compounds derived from can be considered for the development of antiangiogenic drug candidates by targeting VEGFR-2.
血管生成在肿瘤发生过程中起着关键作用，因为它为新生长的实体瘤提供必要的血液供应。它有助于维持肿瘤微环境，促进肿瘤的发展、进展和转移。血管内皮生长因子（VEGF）与内皮细胞上的酪氨酸激酶受体VEGFR-2相互作用，发挥其促血管生成活性。因此，靶向VEGFR-2信号通路被认为是抑制血管生成从而治疗癌症的一种有前景的策略。本研究旨在鉴定从药用植物中提取的能有效与VEGFR-2结合的生物活性化合物。首先使用DataWarrior程序（5.5.0版）筛选该药用植物的生物活性化合物的物理化学性质。最后，选择了17种符合Lipinski五规则且具有良好类药性的化合物进行分子对接研究。分子对接结果表明，配体阿吗灵、1,2-二氢沃米西宁、萝芙辛、育亨宾、阿马林和罂粟碱与靶标VEGFR-2受体强烈相互作用。氢键和疏水相互作用稳定了这些化合物与VEGFR-2的相互作用。这些化合物表现出良好的类药性质且无明显毒性。因此，本研究结果表明，该药用植物衍生的化合物可考虑用于开发靶向VEGFR-2的抗血管生成候选药物。
