title: Benzimidazole-Based Quinazolines: In Vitro Evaluation, Quantitative Structure-Activity Relationship, and Molecular Modeling as Aurora Kinase Inhibitors.
abstract: A series of benzimidazole-based quinazoline derivatives with different substitutions of primary and secondary amines at the C2 position (1-12) were evaluated for their Aurora kinase inhibitory activities. All compounds except for 3 and 6 showed good activity against Aurora kinase inhibitors, with IC50 values in the range of 0.035-0.532 μM. The ligand efficiency (LE) of the compounds with Aurora A kinase was also determined. The structure-activity relationship and the quantitative structure-activity relationship revealed that the Aurora inhibitory activities of these derivatives primarily depend on the different substitutions of the amine present at the C2 position of the quinazoline core. Molecular docking studies in the active binding site also provided theoretical support for the experimental biological data acquired. The current study identifies a novel class of Aurora kinase inhibitors, which can further be used for the treatment of cancer.
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala, India.
authors.forename: Alka
authors.initials: A
authors.lastname: Sharma
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Luxami
authors.affiliation: Department of Biotechnology, Thapar University, Patiala, India.
authors.forename: Sanjai
authors.initials: S
authors.lastname: Saxena
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala, India.
authors.forename: Kamaldeep
authors.initials: K
authors.lastname: Paul
mesh_terms: D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000737:chemistry; D064127:Aurora Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001562:Benzimidazoles; D011799:Quinazolines; D064096:Aurora Kinase A; D064127:Aurora Kinases
keywords: Aurora kinase inhibitor; Molecular modeling; Quantitative structure-activity relationship; Quinazoline-benzimidazole; Structure-activity relationship