Screening of some major phytoconstituents as potential VEGFR-۲ inhibitors from Cissus Verticillata

Angiogenesis plays a crucial role in cancer progression and is primarily regulated by vascular endothelial growth factor receptor-۲ (VEGFR-۲), making it a key therapeutic target in cancer treatment. The present study aimed to screen the major phytoconstituents of Cissus verticillata as potential VEGFR-۲ inhibitors using an in-silico approach. Sixteen compounds were selected and subjected to molecular docking against VEGFR-۲ (PDB ID: ۶GQO) using PyRx. The docking results revealed that the native ligand exhibited a binding affinity of −۹.۴ kcal/mol. Among the phytoconstituents, dihydrokaempferol (−۹.۶ kcal/mol) and taxifolin (−۹.۵ kcal/mol) exhibited the highest binding affinities, followed by ۳-p-coumaroylquinic acid (−۸.۹ kcal/mol) and rutin (−۸.۴ kcal/mol). Similar to the native ligand, these compounds formed strong hydrogen bond interactions with key residues, such as GLU۸۸۵, ASP۱۰۴۶, and CYS۹۱۹, indicating stable binding within the active site. ADMET analysis using SwissADME and ADMETlab ۳.۰ demonstrated that most compounds possessed acceptable pharmacokinetic profiles. The molecular weight ranged from ۱۵۴.۰۳ to ۶۲۲.۲۸ Da, while the TPSA values varied from ۵۷.۵۳ to ۲۷۱.۲ Ų. Smaller molecules, such as p-coumaric acid, showed better permeability, whereas glycosylated compounds, such as rutin, exhibited high polarity but acceptable intestinal absorption. Overall, dihydrokaempferol and taxifolin emerged as the most promising VEGFR-۲ inhibitors, with favorable binding and ADMET properties. These findings provide a basis for further experimental validation and the development of plant-based anti-angiogenic agents.

کلیدواژه ها:

Cissus verticillata ، VEGFR-۲ ، Molecular docking ، ADMET analysis ، Anti-angiogenic activity