مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
inhibitory effects of different phytochemicals on VEGFR-2
inhibitory effects of different phytochemicals on VEGFR-2
Tara Azizi,1,*Aynaz Abedini Shoae,2Sepideh Haghighi,3
1. Islamic Azad University Tehran Central Branch 2. Islamic Azad University Tehran Central Branch 3. Islamic Azad University Tehran Central Branch
Introduction: Vascular endothelial growth factor receptor-2 (VEGFR-2), a receptor tyrosine kinase (RTK), plays an important part in regulating angiogenesis and tumor growth. Excessive activation of VEGFR-2 is strongly linked to cancer initiation and metastasis. Tyrosine kinase inhibitors (TKIs) therefore seem to be a viable therapeutic strategy. This study attempted a comparative investigation of four phytochemicals—curcumin, resveratrol, quercetin, and genistein—with reported anticancer potential through molecular docking to identify the most potent inhibitor of VEGFR-2.
Methods: Three-dimensional structure of VEGFR-2 (PDB ID: 4asd) and selected phytochemicals were retrieved from the Protein Data Bank and Pubchem, respectively. Preparation of structure was done using Chimera. Binding sites were predicted using CASTp and Proteins.Plus servers. Blind and site-specific docking simulations were performed using AutoDock Vina, and interaction analysis was done by PyMOL and Protein-Ligand Interaction Profiler.
Results: All the phytochemicals exhibited sufficient inhibitory activity against VEGFR-2. Curcumin exhibited high binding affinity (-8.2 kcal/mol) with 8 hydrophobic contacts (with LYS 868, GLU 885, ILE 888, LUE 889, VAL 889, VAL 916, and LEU 1035), which provided the most stable complex. Quercetin established maximum hydrogen bonds (two) with hydrophobic contacts. Resveratrol possessed the minimum binding energy (-8.48 kcal/mol) with one hydrogen bond, which was another possible inhibitor. Genistein possessed a single hydrogen bond and 5 hydrophobic contacts. Overall, curcumin exhibited the most potent inhibitory.
Conclusion: This study demonstrates the worth of phytochemicals, including curcumin and resveratrol, as prospective VEGFR-2 inhibitors worth their while. These phytochemicals may be valuable as leads for the synthesis of novel anticancer agents targeted against tyrosine kinase pathways.