Unexplored Enigma in Flemingins against Cholangiocarcinoma: A Network Pharmacology and Molecular Docking Approach to Predict Molecular Mechanisms

Cholangiocarcinoma (CCA) is a fatal malignancy with limited therapeutic options, underscoring the urgent need for novel treatment strategies. Flemingin chalcone compounds derived from Flemingia grahamiana have emerged as promising candidates with potential anticancer properties. This study aimed to explore the therapeutic potential of Flemingins A, B, and C against CCA through an integrated approach combining network pharmacology and molecular docking. Network pharmacology was utilized to identify key molecular targets and signaling pathways associated with the anticancer activity of flemingins. Molecular docking studies were conducted to evaluate the binding interactions between the identified targets. Compound-target network analysis revealed complex interactions with an average node degree of ۲.۱, indicating substantial connectivity between the compounds and their predicted targets. Protein–protein interaction (PPI) analysis highlighted critical targets, including MAPK۳, PIK۳CD, SRC, and STAT۳. Functional enrichment analysis further revealed that flemingins modulate several oncogenic pathways, notably EGFR, PI۳K-AKT, and JAK-STAT signaling. Molecular docking studies validated the binding affinities of Flemingins to the predicted targets, with Flemingin A demonstrating strong interactions, including binding energies of -۱۰.۳ kcal/mol for MAPK۳, -۹.۶ kcal/mol for SRC, -۹.۳ kcal/mol for PIK۳CD, and -۷.۹ kcal/mol for STAT۳. These results suggest a multi-target, multi-pathway mechanism underlying the potential anticancer effects of Flemingins in CCA. This computational investigation provides a comprehensive insight into the molecular basis of the therapeutic potential of flemingins against CCA. Although the results are promising, further experimental validation via preclinical and clinical studies is essential to verify their efficacy and pave the way for future flemingin-based therapeutic strategies in CCA management.

کلیدواژه ها:

cholangiocarcinoma ، Flemingins ، network pharmacology ، Molecular docking ، EGFR Signaling