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

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. Method: 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.