Honeymae C. Alos, Junie B. Billones*, Ross D. Vasquez and Agnes L. Castillo Pages 159 - 178 ( 20 )
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.
ADMET, alpinumisoflavone, angiogenesis, anti-cancer, Matrix Metalloproteinase-9 (MMP-9), molecular docking, vascular endothelial growth factor receptor-2.
The Graduate School, University of Santo Tomas, Manila, OVPAA-EIDR, Department of Physical Sciences and Mathematics, College of Arts and Sciences, University of the Philippines Manila, Manila, The Graduate School, University of Santo Tomas, Manila, The Graduate School, University of Santo Tomas, Manila