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Updated: Jun 28, 2025
Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
Exploring the anticancer potential of fluoro flavone analogues: insights from molecular docking and dynamics studies
Ipsa A Singh1, Kiran Bharat Lokhande1,2, K Venkateswara Swamy3
1Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
Abstract:
Aurora Kinase B belongs to the serine kinase family. It plays an essential role in cell division and participates in mitosis and chromatid segregation. Overexpression, polymorphism, and splicing variants in the protein lead to tumorigenesis, leading to cancer. Flavones belong to the class of flavonoids and are derived from plants and show anti-cancer activities. Fluoro flavones and their analogs are taken from the PubChem database, resulting in 3882 compounds which is 90% similar to the fluoro flavones. Lipinski's rule of five, REOS and PAINS drug-like filters were applied which resulted 2448 compounds. These compounds are docked with Aurora Kinase B using SP and XP modules of Glide software. The best binding scores for SP docking were - 9.153 kcal/mol for the compound with CID: 44298667, and XP docking was - 10.287 kcal/mol with CID: 101664315. Enrichment calculations were done using Aurora Kinase B's decoys to validate the docking result. The resulting R2 = 0.96 from enrichment calculations suggests that the docking protocol is valid. The SP and XP docking lead compounds and the Fluoro flavone were subjected to 100 ns MD simulation to probe the protein-ligand complex stability. Also, the binding free energies between the Aurora kinase B and lead compounds were computed by Prime MM/GBSA module. The result suggests that the lead compounds bind more strongly with Aurora Kinase B than the Fluoro flavone. These lead compounds can be further evaluated in vitro and in vivo and can be used as future novel drugs for the curation of cancer.
Insights
This study identifies novel fluoro flavone analogs with strong binding affinity to Aurora Kinase B, a key protein in cell division and cancer development. These compounds show potential as new anti-cancer drugs.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Aurora Kinase B is a serine kinase crucial for cell division, and its dysregulation is linked to cancer.
- Flavones, plant-derived flavonoids, exhibit anti-cancer properties.
- Identifying novel inhibitors for Aurora Kinase B is a promising strategy for cancer therapy.
Purpose of the Study:
- To computationally screen fluoro flavone analogs for potential inhibition of Aurora Kinase B.
- To identify lead compounds with high binding affinity and stability to Aurora Kinase B.
- To evaluate the potential of these compounds as novel anti-cancer drug candidates.
Main Methods:
- Virtual screening of fluoro flavone analogs from the PubChem database.
- Application of drug-likeness filters (Lipinski's rule of five, REOS, PAINS).
- Molecular docking studies using Glide software (SP and XP modules).
- Validation of docking results through enrichment calculations.
- Molecular dynamics (MD) simulations and binding free energy calculations (MM/GBSA).
Main Results:
- 2448 compounds passed drug-likeness filters from an initial set of 3882.
- Top compounds identified with significant binding scores: CID 44298667 (SP docking: -9.153 kcal/mol) and CID 101664315 (XP docking: -10.287 kcal/mol).
- Enrichment calculations confirmed the validity of the docking protocol (R² = 0.96).
- MD simulations and MM/GBSA analysis indicated stronger binding of lead compounds to Aurora Kinase B compared to fluoro flavone.
- The protein-ligand complexes demonstrated stability over 100 ns MD simulations.
Conclusions:
- Novel fluoro flavone analogs exhibit potent inhibitory activity against Aurora Kinase B.
- The identified lead compounds demonstrate favorable binding affinity and stability.
- These compounds represent promising candidates for further in vitro and in vivo evaluation as novel anti-cancer therapeutics.
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