title: Virtual screening and discovery of novel aurora kinase inhibitors.
abstract: 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 1.324 nM and 5.785 µM for breast cell line and colorectal cell line studies, respectively.
authors.forename: R
authors.initials: R
authors.lastname: Raghu
authors.forename: Vinod
authors.initials: V
authors.lastname: Devaraji
authors.forename: K
authors.initials: K
authors.lastname: Leena
authors.forename: S D
authors.initials: SD
authors.lastname: Riyaz
authors.forename: Polavaru Baby
authors.initials: PB
authors.lastname: Rani
authors.forename: B Suneel
authors.initials: BS
authors.lastname: Kumar
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Naik
authors.forename: P K
authors.initials: PK
authors.lastname: Dubey
authors.forename: Devadasan
authors.initials: D
authors.lastname: Velmurugan
authors.affiliation: Department of Bioinformatics and Biotechnology, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India-173 215. rraghu1@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: Vijayalakshmi
mesh_terms: D064127:Aurora Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013055:Spectrophotometry, Infrared
chemical_list: D001578:Benzopyrans; D007211:Indoles; D047428:Protein Kinase Inhibitors; D064127:Aurora Kinases