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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

Elsherbeny, Mohamed H.; Ammar, Usama M.; Abdellattif, Magda H.; Abourehab, Mohammed A. S.; Abdeen, Ahmed; Ibrahim, Samah F.; Abdelrahaman, Doaa; Mady, Wessam; Roh, Eun Joo; Elkamhawy, Ahmed


Mohamed H. Elsherbeny

Magda H. Abdellattif

Mohammed A. S. Abourehab

Ahmed Abdeen

Samah F. Ibrahim

Doaa Abdelrahaman

Wessam Mady

Eun Joo Roh

Ahmed Elkamhawy


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 6e (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 6e over 14 kinases to evaluate its selectivity profile. Further cell cycle and apoptosis analysis were evaluated for compound 6e over the MCF-7 cell line at its IC50 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 6e 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 6e 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.

Journal Article Type Article
Acceptance Date Jun 7, 2022
Online Publication Date Jun 10, 2022
Publication Date Jun 10, 2022
Deposit Date Dec 11, 2022
Publicly Available Date Dec 12, 2022
Journal Life
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 12
Issue 6
Article Number 876
Keywords quinazoline; Aurora A; kinases; anticancer; molecular docking; cell cycle; apoptosis
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