Unexplored Enigma in Flemingins against Cholangiocarcinoma: A Network Pharmacology and Molecular Docking Approach to Predict Molecular Mechanisms
نویسندگان
1 Department of Pharmaceutical Chemistry, Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India
2 Anurag University, Venkatapur, Ghatkesar, Medchal-Malkajgiri District, Telangana 500088, India
3 Faculty of Pharmaceutical Science, Assam down town University, Sankar Madhab Path, Gandhi Nagar, Panikhaiti, Guwahati, Assam, India
4 Raghu college of pharmacy, Dakamarri, Bhimunipatnam, Vishakapatnam 531162, India
5 Jeypore College of Pharmacy, Ronadapalli, Koraput, Odisha, India
6 Department of Pharmacology, Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India
7 Department of Pharmaceutical Chemistry, Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India
8 Department of Pharmaceutical Chemistry, Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad, Maharashtra, India
9 Department of Pharmacology, SOAHS, Mallareddy University, Maisammaguda, Dulapally, Hyderabad, Telangana 500100, India
10 Department of Pharmaceutical Chemistry, Narayan Institute of Pharmacy, Gopal Narayan Singh University, Jamuhar, Sasaram (Rohtas) Bihar - 821305, India
doi
10.48309/chemm.2025.511214.1915چکیده
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 2.1, indicating substantial connectivity between the compounds and their predicted targets. Protein–protein interaction (PPI) analysis highlighted critical targets, including MAPK3, PIK3CD, SRC, and STAT3. Functional enrichment analysis further revealed that flemingins modulate several oncogenic pathways, notably EGFR, PI3K-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 -10.3 kcal/mol for MAPK3, -9.6 kcal/mol for SRC, -9.3 kcal/mol for PIK3CD, and -7.9 kcal/mol for STAT3. 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.
