2-(3-Bromophenyl)-8-fluoroquinazoline-4-carboxylic Acid as a Novel and Selective Aurora A Kinase Inhibitory Lead with Apoptosis Properties: Design, Synthesis, In Vitro and In Silico Biological Evaluation.

New quinazoline derivatives were designed based on the structural modification of the reported inhibitors to enhance their selectivity toward Aurora A. The synthesized compounds were tested over Aurora A, and a cytotoxicity assay was performed over NCI cell lines to select the best candidate for further evaluation. Compound (2-(3-bromophenyl)-8-fluoroquinazoline-4-carboxylic acid) was the most potent compound among the tested derivatives. A Kinase panel assay was conducted for compound over 14 kinases to evaluate its selectivity profile. Further cell cycle and apoptosis analysis were evaluated for compound over the MCF-7 cell line at its IC of 168.78 µM. It arrested the cell cycle at the G1 phase and induced apoptosis. Molecular docking was performed to explore the possible binding mode of compound into the active site. It showed significant binding into the main pocket in addition to potential binding interactions with the key amino acid residues. Accordingly, compound can be considered a potential lead for further structural and molecular optimization of the quinazoline-based carboxylic acid scaffold for Aurora A kinase selective inhibition with apoptosis properties.