In silico exploration and identification of key bioactive compounds of the molecular targets of Piper guineense in colon cancer through network pharmacology, and molecular docking
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Abstract
Colon cancer is a severe and rapidly progressing disease that represents a substantial global health challenge. Piper guineense is a plant with anticancer potential that requires experimental validation; however, its molecular mechanisms against colon cancer remain poorly understood. This research utilized a network pharmacology approach combined with molecular docking to explore possible therapeutic mechanisms. The bioactive compounds were identified using gas chromatography–mass spectrometry (GC–MS). Colon cancer–related genes were obtained from the GeneCards and DisGeNET databases, while predicted targets of the identified compounds were generated through SwissTarget Prediction. Overlapping targets between compounds and disease genes were identified and used to construct protein–protein interaction network via STRING. The network was visualized in Cytoscape, hub genes were screened using CytoHubba, and functional enrichment analysis was conducted using Gene Ontology and KEGG pathway databases. Molecular docking was performed using PyRx software. A total of 21 compounds from GC-MS corresponding to 452 non-redundant targets were identified, and 7,332 colon cancer targets were obtained from the databases. Five hub genes were identified as key targets: EGFR, MAP2K1, SRC, KDR, and PIK3CA. Molecular docking analysis demonstrated that α-selinene bound to EGFR, MAP2K1, SRC, and PIK3CA with docking scores of −7.6, −7.7, −5.1, and −7.5 kcal/mol, respectively, while β-selinene had scores of −7.5, −7.7, −5.4, and −7.6 kcal/mol with the same targets. β-humulene exhibited a strong docking score of −8.7 kcal/mol towards KDR. The α and β-selinene, and humulene showed better docking scores in comparison with 5-fluorouracil, which contributes to its anticancer potential.
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