Applied Sciences
| Open Access |
DOI: Integrative Network Pharmacology and Structure-Based Molecular Docking for the Computational Identification of CHEK2-Targeting Phytochemicals in Triple-Negative Breast Cancer
Sana Rahman , Amity Institute of Biotechnology, Amity University Uttar Pradesh Lucknow Campus, Lucknow, UP, India Shrijal Singh , Amity Institute of Biotechnology, Amity University Uttar Pradesh Lucknow Campus, Lucknow, UP, India Sanjana Mishra , Amity Institute of Biotechnology, Amity University Uttar Pradesh Lucknow Campus, Lucknow, UP, India Prachi Srivastava , Amity Institute of Biotechnology, Amity University Uttar Pradesh Lucknow Campus, Lucknow, UP, IndiaAbstract
Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer and it is very difficult to treat because it lacks the common hormone receptors which is used in targeted therapies. The main aim of this study was identifying an important target gene involved in TNBC and to evaluate the potential of selected natural compounds using computational approaches. Genes related to TNBC they were collected from the Gene Cards database, and the most relevant genes were selected for further analysis. A protein-protein interaction (PPI) network was then constructed and analysed using Cytoscape software. Based on network parameters such as degree and betweenness centrality, CHEK2 (Checkpoint kinase 2) was identified as a main target gene because of its strong interactions with other associated genes. Five phytochemicals-curcumin, piperine, cinnamaldehyde, 6-gingerol, and allicin were selected from previously published studies for further investigation. The three-dimensional structure of the CHEK2 protein was obtained using PDB database and evaluated before docking analysis. Molecular docking was then performed using the Dock Thor with a blind docking approach to study the interaction of these compounds with the target protein. The docking results showed that all phytochemicals exhibited stable binding with the protein. Among them, curcumin demonstrated the highest binding affinity (−9.386 kcal/mol), followed by piperine (−8.847 kcal/mol), cinnamaldehyde (−8.12 kcal/mol), 6-gingerol (−7.933 kcal/mol), and allicin (−7.855 kcal/mol). These results indicates that curcumin may have stronger interaction potential with the CHEK2 protein. In conclusion, the study highlights the importance of network-based target identification and it supports the potential role of natural phytochemicals, particularly curcumin, in TNBC treatment. Further experimental validation is required to confirm these findings.
Keywords
TNBC, CHEK2, molecular docking, phytochemicals, network pharmacology, curcumin
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