Structure-Based In Silico Drug Design and Docking Studies of Plant Phytochemicals as Fibroblast Growth Factor Receptor Inhibitors in Oral Squamous Cell Carcinoma

Background: Oral squamous cell carcinoma (OSCC) accounts for 90% of all head and neck cancer and the fibroblast growth factor receptors (FGFR) was recognized as a therapeutic target in OSCC. Objectives: In this study, bioactive compounds from Chimaphila umbellata were screened for their potential interaction towards FGFR with the help of bioinformatics tools. Methods: Drug-likeness and pharmacokinetics properties of phytochemicals were analyzed using online web server Swiss ADME. Expression profiling and protein-protein interaction (PPI) analyses were conducted using GEPIA and String. Docking was carried out in Autodock Tools 1.5.7 and Toxicity was predicted from ProTox II. The biological activity spectrum (BAS) was predicted using the PASS online web server. Results: About 15 compounds selected from C. umbellata was screened and out of which, 13 showed drug-likenesses and pharmacokinetics. FGFR4 demonstrated connections with other genes in the PPI network. Among 13 compounds, 4 showed the best affinity towards FGFR. Finally two compounds namely arbutin and kaempferol possess oral bioavailability with no predicted toxicity. BAS prediction showed antineoplastic activity of the leads. Conclusion: Two leads were identified as FGFR4 inhibitor through in silico . These leads should be tested in vitro and in vivo studies to confirm their action OSCC.