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Benzimidazole‐Based Quinazolines: In Vitro Evaluation, Quantitative Structure–Activity Relationship, and Molecular Modeling as Aurora Kinase Inhibitors
Author(s) -
Sharma Alka,
Luxami Vijay,
Saxena Sanjai,
Paul Kamaldeep
Publication year - 2016
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201500281
Subject(s) - benzimidazole , quinazoline , chemistry , docking (animal) , kinase , aurora kinase , structure–activity relationship , stereochemistry , molecular model , in vitro , biological activity , biochemistry , combinatorial chemistry , cell , organic chemistry , medicine , cell cycle , nursing
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 IC 50 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.