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Updated: Sep 21, 2025
Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
Published on: February 21, 2019
Exploring the Activity of Fungal Phenalenone Derivatives as Potential CK2 Inhibitors Using Computational Methods
Sabrin R M Ibrahim1,2, Alaa A Bagalagel3, Reem M Diri3
1Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia.
Abstract:
Cancer represents one of the most prevalent causes of global death. CK2 (casein kinase 2) activation boosted cancer proliferation and progression. Therefore, CK2 inhibition can have a crucial role in prohibiting cancer progression and enhancing apoptosis. Fungi have gained vast interest as a wealthy pool of anticancer metabolites that could particularly target various cancer progression-linked signaling pathways. Phenalenones are a unique class of secondary metabolites that possess diverse bioactivities. In the current work, the CK2 inhibitory capacity of 33 fungal phenalenones was explored using computational studies. After evaluating the usefulness of the compounds as enzyme inhibitors by ADMET prediction, the compounds were prepared for molecular docking in the CK2-α1 crystal structure (PDB: 7BU4). Molecular dynamic simulation was performed on the top two scoring compounds to evaluate their binding affinity and protein stability through a simulated physiological environment. Compound 19 had a superior binding affinity to the co-crystallized ligand (Y49). The improved affinity can be attributed to the fact that the aliphatic chain makes additional contact with Asp120 in a pocket distant from the active site.
Insights
This study explored fungal phenalenones as casein kinase 2 (CK2) inhibitors for cancer therapy. Compound 19 demonstrated superior binding affinity, suggesting potential for novel anticancer drug development.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Computational Biology
Background:
- Cancer is a leading global cause of death, with casein kinase 2 (CK2) activation promoting its proliferation.
- CK2 inhibition is a promising strategy to impede cancer progression and induce apoptosis.
- Fungal metabolites, particularly phenalenones, are recognized for their diverse bioactivities and potential anticancer properties.
Purpose of the Study:
- To investigate the CK2 inhibitory potential of 33 fungal phenalenones using computational methods.
- To evaluate the drug-likeness and binding interactions of these compounds with CK2-α1.
- To identify promising phenalenone derivatives for further development as anticancer agents.
Main Methods:
- Computational screening of 33 fungal phenalenones for CK2 inhibition.
- ADMET prediction to assess compound usability as enzyme inhibitors.
- Molecular docking against the CK2-α1 crystal structure (PDB: 7BU4).
- Molecular dynamic simulations for top-scoring compounds to assess binding stability and affinity.
Main Results:
- Compound 19 exhibited superior binding affinity to CK2-α1 compared to the co-crystallized ligand (Y49).
- The enhanced binding of Compound 19 is attributed to additional interactions of its aliphatic chain with Asp120.
- Molecular dynamics simulations confirmed the stability and strong binding of Compound 19 within a pocket distant from the active site.
Conclusions:
- Fungal phenalenones represent a viable class of compounds for targeting CK2 in cancer therapy.
- Compound 19 shows significant potential as a lead compound for developing novel CK2 inhibitors.
- Further research into Compound 19 could lead to new therapeutic strategies against cancer.
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