In silico discovery of potential vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors from the phytochemicals of Sonneratia alba (Pagatpat)

One potential strategy for cancer treatment is to prevent neovascularization. A well-targeted approach blocks VEGFR2, inhibiting the growth of new tumor vasculature. In this study, we report the identification of potential VEGFR2 inhibitors from phytochemicals previously extracted from Sonneratia alba, a mangrove species native to the Philippines, using molecular docking simulations followed by drug-likeness and ADME/Tox prediction. Thirty-two phytochemicals identified from various parts of S. alba were virtually docked onto the VEGFR2 binding site. Luteolin, ⍺-amyrin cinnamate, and ꞵ-amyrin cinnamate exhibited docking scores comparable to the drug control Axitinib. The drug-likeness property prediction revealed luteolin as the sole phytochemical predicted to have high bioavailability. In silico ADMET prediction demonstrated that luteolin has higher human intestinal absorption, is firmly bound to plasma protein, and poses no toxicity risks. Furthermore, luteolin also exhibited high permeability across the gastrointestinal tract but no passive permeability across the blood–brain barrier. Through in silico techniques, luteolin was identified as the only compound from S. alba with adequate and significant potential of developing into a VEGF inhibitor drug, as exemplified by its good bioavailability, higher gastrointestinal absorption, strong binding affinity to plasma protein, and good permeability through the gastrointestinal tract. The findings of this investigation may help validate the in vitro and in vivo anticancer properties of luteolin, as described in several peer-reviewed articles.