European Journal of Medicinal Plants

Background: Cancer is one of the most destructive diseases, claiming millions of lives every year. Oncogenic proteins cause uncontrolled cell growth and potentially result in cancer and are now targets of cancer therapies. The use of in silico molecular biology techniques has sped up drug discovery and development.

Aim: The present study elucidates the pharmacokinetic and anticancer properties of ligands from common foods, spices and herbs through bioinformatics techniques.

Methodology: This research investigated the pharmacokinetic and anticancer properties of 60 phytochemicals (ligands) that are found in commonly consumed foods, fruits, vegetables, spices and medicinal plants, through standard in silico molecular biology techniques. The ligands were screened for their physicochemical properties, drug-likeness (including the  Lipinski's Rule of Five), potential drug-drug interactions, and PAINS and Brenk alerts, using the SwissADME software. Thirteen ligands passed Lipinski's rule and the PAINS and Brenk alert tests. They were therefore used for the anticancer studies.  The 13 ligands were docked with 10 oncogenic proteins by using the SwissDock software. Two reference anticancer drugs per oncogenic protein, totaling 20 reference drugs, were used as standard drugs for the anticancer molecular docking study. Selected docked protein ligand complexes were visualized for protein-ligand interactions via the Biovia Discovery Studio Visualizer. 

Results: Eight of the ligands (Acetogenin, Annonacin, Annopentocin A, Apigenin, Kaempferol, Muricatonin A, Odoratin, & Scopadulciol) exhibited good dockings (binding energies of less than -6.0 kcal/mol) with at least one of the oncogenic proteins. Visualized protein-ligand interactions included hydrogen bonds, Pi-Alkyl, Pi-Sigma, Pi-Pi T-shaped, Amide-Pi Stacked, and Pi-Sulfur bonds. Many of the ligands exhibited good dockings with several oncogenic proteins. Three ligands (apigenin, kaempferol and scopadulciol) were exceptionally excellent in their dockings with most of the oncogenic proteins and they are recommended for further research, including molecular dynamics simulations and translational research studies. Likewise, the Arg V23, His V27, Leu Y174, Pro Y173, and Pro V28 residues of VEGF, and the Asn A557 residue of FGFR4 exhibited molecular interactions with several ligands tested.

Conclusion: This study has identified potential anticancer agents exhibiting favorable pharmacokinetic properties and minimal toxicity using bioinformatic approaches. Given that most anticancer drugs are associated with adverse effects on healthy cells, resulting in various side effects, the discovery of alternatives with reduced or negligible side effects represents a significant advancement. We recommend that further investigations, including molecular dynamics simulations and translational research studies, be carried out on the eight ligands which have demonstrated promising pharmacokinetic profiles and anticancer activity. Additionally, it is advisable to incorporate foods, spices, and herbs containing these ligands into regular diets, as they passed pharmacokinetic and toxicity assessments and exhibited notable anticancer properties