Exploring the anticancer potential of fluoro flavone analogues: insights from molecular docking and dynamics studies with Aurora Kinase B

Ipsa A Singh; Kiran Bharat Lokhande; K Venkateswara Swamy

doi:10.1007/s40203-024-00200-9

Exploring the anticancer potential of fluoro flavone analogues: insights from molecular docking and dynamics studies with Aurora Kinase B

In Silico Pharmacol. 2024 Apr 7;12(1):26. doi: 10.1007/s40203-024-00200-9. eCollection 2024.

Authors

Ipsa A Singh¹, Kiran Bharat Lokhande^{1

2}, K Venkateswara Swamy³

Affiliations

¹ Bioinformatics Research Laboratory, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India.
² Present Address: Translational Bioinformatics and Computational Genomics Research Lab, Department of Life Sciences, Shiv Nadar Institution of Eminence, Gautam Buddha Nagar, Greater Noida, UP India.
³ Drug Discovery Group, MIT School of Bioengineering Sciences & Research, MIT Art, Design and Technology University, Pune, 412201 India.

PMID: 38596365
PMCID: PMC10999403 (available on 2025-04-07)
DOI: 10.1007/s40203-024-00200-9

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.

Keywords: Aurora kinase B; Cancer; Fluoro flavones; MD simulation; Molecular docking.

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