Browsing by Author "Kariyawasam, K. B. G. A. S."

Filter results by typing the first few letters
Now showing 1 - 1 of 1
  • Thumbnail Image
    Item
    In-silico insights of effects of major phytoconstituents in pomegranate on prostate cancer
    (Faculty of Science, University of Kelaniya Sri Lanka, 2024) Kariyawasam, K. B. G. A. S.; Dahanayake, J. N.
    Among diverse cancer types, prostate cancer is the second most common non-cutaneous cancer type in males. Various treatment options at present target AR (Androgen Receptor) signaling cascade, EGFR (Epidermal Growth Factor Receptor) inhibition, and PI3k signal transduction mechanism. The ultimate medications for prostate cancer are xenobiotics which show diverse side effects on the human body. Consequently, scientists’ approach is to develop new medications derived from phytoconstituents originating from different plant species. In Ayurvedic and traditional medication practices, it was believed that phytoconstituents present in pomegranate (Punica granatum) have antioxidant, antiinflammatory, and anti-tumor properties. In this research, the agonistic, antagonistic, and inhibitory nature of polyphenols and flavones present in pomegranate were investigated and compared with reference drugs that are commercially available to ascertain the results. The in-silico study assessed the effectiveness of major seven secondary metabolites present in pomegranate (catechin, citric acid, ellagic acid, ellagic acid-4-O-xylopyranoside, gallic acid, quercitrin, and vanillic acid) against AR and EGFR. The geometry-optimized molecules were docked using Autodock 4.2.6 with their respective protein targets. The scoring functions of docking were utilized to determine free binding energies and inhibition constants. To enhance a better understanding, two-dimensional and three-dimensional aspects of interactions and the interacting residues were visualized by Discovery Studio software. The natural ligands: testosterone and xenobiotics (Bicalutamide, Enzalutamide, Gefitinib and Erlotinib) were used as reference compounds. The results indicated that binding free energies for AR were between -5 to - 12 kcal/mol and for EGFR -3 to -7 kcal/mol. The lowest Inhibition constant values (Ki) were in the nanomolar range for AR and in the micromolar range for EGFR. The lowest binding energies for AR ranged as testosterone (-11.78 kcal/mol) < ellagic acid-4-O-xylopyranoside (-8.76 kcal/mol) < catechin (-8.57 kcal/mol) < bicalutamide (-8.33 kcal/mol) < ellagic acid (-8.12 kcal/mol) < enzalutamide (-7.96 kcal/mol) in ascending order. The lowest binding energies for EGFR ranged as gefitinib (-6.61 kcal/mol) < catechin (-5.98 kcal/mol) < ellagic acid (-5.51 kcal/mol) < ellagic acid-4-O-xylopyranoside (-5.18 kcal/mol) < erlontib (-4.75 kcal/mol) in ascending order. It was evident that the potential of ellagic acid-4-O-xylopyranoside, ellagic acid, and catechin compounds to act as a kind of novel inhibitor and an insight into the designing of structurally novel potent anti-carcinogenic which will be more economical and beneficial in the pharmaceutical industry.