title: Theoretical Studies on Azaindoles as Human Aurora B Kinase Inhibitors: Docking, Pharmacophore and ADMET Studies.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Vikas College of Pharmacy, Jangaon, Warangal, Telangana, India. mailme2rajashekar@gmail.com.
authors.forename: Rajashekar
authors.initials: R
authors.lastname: Vadlakonda
authors.affiliation: Department of Pharmaceutical Chemistry, Balaji Institute of Pharmaceutical Sciences, Laknepally, Narsampet, Warangal, Telangana, India.
authors.forename: Raghunandan
authors.initials: R
authors.lastname: Nerella
authors.affiliation: Department of Bioinformatics, Averinbiotech, 208, 2nd Floor, Windsor Plaza, Nallakunta, Hyderabad, Telangana, India.
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Enaganti
mesh_terms: D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D008024:Ligands; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship; D018675:Toxicity Tests
chemical_list: D007211:Indoles; D008024:Ligands; D047428:Protein Kinase Inhibitors; C576921:AURKB protein, human; D064107:Aurora Kinase B
keywords: Aurora kinases; Cancer; Cell cycle; Docking; Genomic stability; Pharmacophore