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Volume 31, Issue 10
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Background

About 10-15% of all breast cancers comprise triple-negative breast cancer (TNBC), defined as cancer cells that lack ER, PR, and HER2 protein receptors. Due to the absence of these receptors, treating TNBC using conventional chemotherapy is challenging and, therefore, requires the discovery of novel chemotherapeutic agents derived from natural sources.

Objective

The current work was intended to study the potential phytochemicals of Ajwa dates ( L.) with the predicted potential targets (namely, Akt and PI3K) to determine possible TNBC inhibitors.

Methods

We harnessed network pharmacology, molecular docking, drug-likeness studies, Molecular Dynamics (MD) simulation, and binding free energy (MM-GBSA) calculation to get phytochemicals with potential effects against TNBC. Firstly, molecular docking was performed on 125 phytochemicals against the Akt and PI3K proteins utilizing PyRx. Then, the phytochemicals with the highest binding affinity (≤ -8.1 kcal/mol) were examined for drug-likeness and toxicity profiles. Finally, phytochemicals with optimal drug-likeness and toxicity profiles were studied by Molecular Dynamics (MD) simulation and binding free energy (MM-GBSA) to identify compounds that can form stable complexes.

Results

The results of the network pharmacology revealed that the Akt and PI3K proteins are potential targets of TNBC for the phytochemicals of L. used in this study. The outcomes of molecular docking displayed that among 125 phytochemicals, 42 of them (with a binding affinity ≤ -8.1 kcal/mol) have potentially inhibiting effects on both proteins PI3K and Akt expressed in TNBC. Then, the results of drug-likeness identified seven phytochemicals with optimal pharmacokinetic profiles. Furthermore, toxicity studies showed that three phytochemicals (namely, Chrysoeriol, Daidzein, and Glycitein) did not cause any toxicities. Finally, the Molecular Dynamics (MD) simulation studies and binding free energy (MM-GBSA) verified that Daidzein stayed within the binding cavities of both proteins (Akt and PI3K) by establishing a stable protein-ligand complex during simulation.

Conclusion

Taken together, the current work emphasizes the potential effects of Daidzein from L. against TNBC, and it can be further studied to establish it as a standard chemotherapy for TNBC.

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/content/journals/cpd/10.2174/0113816128348876241017101729
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Network Pharmacology and In silico Elucidation of Phytochemicals Extracted from Ajwa Dates (Phoenix dactylifera L.) to Inhibit Akt and PI3K Causing Triple Negative Breast Cancer (TNBC)
Curr. Pharm. Des. 31, 774 (2025); https://doi.org/10.2174/0113816128348876241017101729
/content/journals/cpd/10.2174/0113816128348876241017101729
/content/journals/cpd/10.2174/0113816128348876241017101729
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  • Article Type:     Research Article
Keyword(s): drug likeness; GO pathway; hub genes; KEGG pathway; molecular docking; molecular dynamics (MD) simulation; Phoenix dactylifera L.; phosphoinositide 3-kinase (PI3K); phytochemicals; protein kinase B (Akt); protein-protein interactions; triple-negative breast cancer (TNBC)

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