Identification of Anticancer Potential of Phytoconstituents of Cuminum cyminum Effective against Hepatocellular Carcinoma Using Computational Approaches

Objective: To explore anticancer agents from Cuminum cyminum against hepatocellular carcinoma.Study Design: In-silico approaches using computational tools to determine the anticancer potential of phytoconstituents of cumin against hepatocellular carcinoma.Place and Duration of Study: This study was conducted from May 2021 to January 2022 at the Department of Bioinformatics and Biosciences of Capital University of Science and Technology, Islamabad, Pakistan.Materials and Methods: In this study, bioactive compounds of Cuminum cyminum representatives of Flavonoids, Phenolic acids, Terpenes, and Glycosides were selected to determine the anticancer potential of these ligands using an in-silico approach.  Virtual screening of these ligands was carried out against the drug target, which was Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2).  To identify novel anticancer bioactive compounds of Cuminum cyminum as potential inhibitors of VEGFR-2, Lipinski rule of five, Pharmacokinetic properties, and molecular docking were performed. Lipinski's rule of five and the Pharmacokinetic properties of ligands were studied through the pkCSM tool. Auto-dock performed molecular docking.Results: From these selected compounds, four ligands showed themselves as hit compounds. Among them, Quercetin was selected as the lead compound in this research against VEGFR-2 because it showed a -10.14 kcal/mol binding score and showed more active results with less toxic effects than the standard drug, which was Lenvatinib. All ligands-protein interaction visualization analyses were performed by PyMol molecular visualization tool and Discovery tool.Conclusion: Quercetin was identified as a lead compound that should be explored as a drug candidate in wet lab analysis to validate its efficacy for the treatment of HCC.