Theoretical Studies on Azaindoles as Human Aurora B Kinase Inhibitors: Docking, Pharmacophore and ADMET Studies
Aurora kinases are the cell cycle mitotic regulators processing multiple functions during cell division. Altered mechanism of these mitotic kinases may contribute to genomic instability that is most often correlated with tumorigenesis, which has been reported in many human cancers. Selective blockage of the aberrantly expressed Aurora kinases has the potential therapeutic assessment to control the deregulated cell cycle machinery and their associated risks of cancer. Using a combination of docking-, ligand- and structure-based pharmacophore strategies, in the present study, we have tried to predict the anticancer potentiality of our synthesized compounds (A1 to A5 and B1 to B9) against human Aurora B kinase. The results revealed that among all the compounds, compound B7 may act as a best candidate to be an agent of the high binding affinity with a score of 113.464 kcal/mol and good pharmacophoric features with acceptable fit values of both ligand- and structure-based pharmacophore models. Consequently, ADMET properties are also calculated to predict the safer efficacy of the compounds.
KeywordsAurora kinases Cancer Cell cycle Docking Genomic stability Pharmacophore
- 1.Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F( (2013) GLOBOCAN 2012 v1.0 cancer incidence and mortality worldwide: IARC CancerBase No. 11. International Agency for Research on Cancer, LyonGoogle Scholar
- 23.Lucena-Araujo AR, de Oliveira FM, Leite-Cueva SD, dos Santos GA, Falcao RP, Rego EM (2011) High expression of AURKA and AURKB is associated with unfavorable cytogenetic abnormalities and high white blood cell count in patients with acute myeloid leukemia. Leuk Res 35:260–264CrossRefPubMedGoogle Scholar
- 27.Batool S, Ferdous S, Kamal MA, Iftikhar H, Rashid S (2013) In silico screening for identification of novel Aurora Kinase inhibitors by molecular docking, dynamics simulations and ligand-based hypothesis approaches. Enzyme Eng 2:106Google Scholar