Screening and Selection of Hispaglabridin B as a Lead Compound in Colon Cancer Treatment: In Silico Approach

Abstract

Introduction: Colon cancer is the third largest cause of cancer-related death according to a survey report by GLOBOCAN 2020. Though several common conditions, including family history and personal health care, are reported as the causes of colon cancer, the real cause of colorectal cancer is unrevealed. Treatment with chemical drugs like 5-fluorouracil in combination with radiation therapy can help to shrink tumor size. Surgical procedures can also be performed at the early stage along with the administration of drugs. However, the available treatment strategies are equally toxic to healthy cells and, in general, are nonspecific. The side effects of chemical drug administration are very devastating. Hence, natural phytochemicals can be a better choice for treating cancer. Materials and methods: In this article, in silico screening of plenty of phytochemicals from 200 different plants was performed. Databases such as PubChem, Drugbank, ChemSpider, eMolecules, and Chembank were used for extracting structures of phytochemicals including flavonoids, alkaloids, peptides, steroids, or any other organic compounds, and used as ligands. Vital proteins involved in colon cancer pathways are extracted from the protein data bank based on the output from the KEGG pathway database and Cytoscape network analysis. AutoDockPyRx Python prescription-0.8 was used to predict the possible ligands and their targets using a structure-based drug discovery approach. Results and Discussion: Hispaglabridin B showed interaction with a maximum number of target proteins at low binding energies. Swiss target prediction was used to find other potent targets for the selected ligand. The binding pocket analysis showed that hispaglabridin B binds to the same position as the known inhibitor of the target protein. The amino acids involved in the protein and hispaglabridin B interaction were also studied. Polar, hydrophobic, hydrogen bond, and charge-based interactions were dominant between hispaglabridin B and its targets. PASS online was used to check the biological potential of hispaglabridin B. The drug likeliness properties and ADME characteristics of hispaglabridin B were checked using DruLiTo and Swiss ADME, respectively. The toxicity of hispaglabridin B was analyzed using preADMET and was found safe. Hispaglabridin B was not available in the drug bank, and its structure was predicted to be an isoflavonoid. Isoflavanols are polycyclic compounds containing a hydroxylated isoflavone skeleton and an aromatic hetero-polycyclic molecular framework. From the literature, the most abundant source of hispaglabridin B was found to be Glycyrrhiza glabra.Conclusion: Hence, it is concluded that hispaglabridin B could be a potential lead for developing an effective colon cancer drug.