Cancer remains one of the major contributors to human mortality and a hazard to human growth. The search for
a new treatment continues unabated. Aurora kinases play an important role in cell cycle, and thus a potential target for the
treatment of cancer. In the present work, we aim to discover potential leads against aurora kinase using various rational
methods of drug discovery. The available crystal complexes of AKs were analyzed for their interactions and quantified
with glide-extra precision (XP) docking. About 20 crystal pdb were selected from the protein databank based on the resolution
factor, R-factor and R-value. And after docking with the native ligands, the RMSD value was calculated, wherein
the protein with the least RMSD was found to be 3UOK which was further used for our screening of small molecules
from the in-house database by molecular docking. Fragments which were found to possess the best interactions were considered
for the synthesis with characterization, and biological activity was carried out against breast cancer and colorectal
cancer cell lines to assess the inhibitory capability of synthesized compounds. Molecule with the molecular id IS2 i.e.
(3E)-3-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2H chromene-2,4(3H)-dione was found to possess inhibitory activity
with an IC50 of 1.324nM and 5.785µM for breast cell line and colorectal cell line studies, respectively.
Keywords: Aurora kinase, cancer, docking, glide score, in-vitro cell line studies, PDB.
Rights & PermissionsPrintExport