Antiangiogenesis Potential of Alpinumisoflavone as an Inhibitor of Matrix Metalloproteinase-9 (MMP-9) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2)

Author(s): Honeymae C. Alos, Junie B. Billones*, Ross D. Vasquez, Agnes L. Castillo

Journal Name: Current Enzyme Inhibition

Volume 15 , Issue 3 , 2019

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Graphical Abstract:


Background: Cancer is a very serious public health problem ranking as the second leading cause of death worldwide. Angiogenesis plays a vital role as a prerequisite for tumor growth and metastasis, and is indispensable in the further stage advancement of cancer.

Objective: Targeting several enzymes and receptors in angiogenesis’ signal transduction pathway will likely offer many more prospects for successful and superior therapeutic intervention.

Methods: Thus, druggable targets in the angiogenesis pathway such as pro-MMP9, MMP-9, EGFR, VEGF-A, VEGFR-1, VEGFR-2, c-MET kinase, KIT kinase, CSF1R, TIE-2, and RET tyrosine kinase were the subject of this molecular docking study involving Alpinumisoflavone (AIF), a multi-targeted natural product with known anticancer activities.

Results: The results showed that AIF exhibited good binding affinity with all the selected key angiogenesis promoting proteins with greatest in silico activity in MMP-9 and VEGFR-2. Moreover, in silico ADMET studies showed that AIF has good intestinal absorption property and solubility, and very low probability of being carcinogenic, mutagenic, and toxic to embryo or fetus.

Conclusion: Molecular docking study revealed that Alpinumisoflavone (AIF) could serve as a promising lead in the development of angiogenesis (multikinase) inhibitor based on its predicted binding affinity with vital angiogenesis targets.

Keywords: ADMET, alpinumisoflavone, angiogenesis, anti-cancer, Matrix Metalloproteinase-9 (MMP-9), molecular docking, vascular endothelial growth factor receptor-2.

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Year: 2019
Page: [159 - 178]
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DOI: 10.2174/1573408016666200123160509
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