Abstract
Aurora kinase is a group of enzymes that belongs to a serine-threonine family and
plays a critical role in cellular division. Aurora Kinase A is overexpressed and
distributed beyond the nucleus and is involved in tumorigenesis. Flavones are a
class of flavonoids that are present in plants that show anticancer activity.
Similar compounds of 2’Fluoroflavones are retrieved from the PubChem
database. Then drug-like filters viz. REOS and PAINS were applied to remove
toxic compounds using Canvas software, resulting in 3882 compounds being
subjected to Glide docking with Aurora kinase A. The lead compounds were
selected on the merit of hydrogen bonding, salt bridge, as well as pi-pi
interactions, 4-(6-Fluoro-4-oxychromen-2yl) benzoic acid, has been found one of
the best molecules from docking studies. The binding mode of the lead compound
with AURKA reveals that the amino acid residues viz, Lys162, Ala213, and His280
are more important for binding with the binding affinity of
-11.760 kcal/mol. The molecular dynamics simulations of
100 ns were done, which shows the mean RMSD value of
1.77 Å for all 3 complexes of the protein and Fluoroflavone and
its analogs. This shows that Fluoroflavone and its 2 best analogs are tightly
attached to the active sites and thus have conformational stability. Our finding
suggests that 4-(6-fluoro-4-oxochromen-2-yl)benzoic acid and
4-(4-Oxochromen-2-yl)benzoate can be further used in vitro and in
vivo experiments and can probably serve as a novel drug for cancer
treatment.
Key words
Aurora kinase A - Fluoroflavones - chemoinformatics - Glide docking - MD simulation
- Enrichment calculations
