Sulfonamide-based 4-anilinoquinoline derivatives as novel dual Aurora kinase (AURKA/B) inhibitors: Synthesis, biological evaluation and in silico insights.

Sulfonamide-based 4-anilinoquinoline derivatives as novel dual Aurora kinase (AURKA/B) inhibitors: Synthesis, biological evaluation and in silico insights. Bioorg Med Chem. 2020 Apr 25;:115525 Authors: Al-Sanea MM, Elkamhawy A, Paik S, Lee K, El Kerdawy AM, Syed Nasir Abbas B, Joo Roh E, Eldehna WM, Elshemy HAH, Bakr RB, Ali Farahat I, Alzarea AI, Alzarea SI, Alharbi KS, Abdelgawad MA Abstract Aurora kinases (AURKs) were identified as promising druggable targets for targeted cancer therapy. Aiming at the development of novel chemotype of dual AURKA/B inhibitors, herein we report the design and synthesis of three series of 4-anilinoquinoline derivatives bearing a sulfonamide moiety (5a-d, 9a-d and 11a-d). The % inhibition of AURKA/B was determined for all target quinolines, then compounds showed more than 50% inhibition on either of the enzymes, were evaluated further for their IC50 on the corresponding enzyme. In particular, compound 9d displayed potent AURKA/B inhibitory activities with IC50 of 0.93 and 0.09 µM, respectively. Also, 9d emerged as the most efficient anti-proliferative analogue in the US-NCI anticancer assay toward the NCI 60 cell lines panel, with broad spectrum activity against different cell lines from diverse cancer subpanels. Docking studies, confirmed that, the sulfonamide SO2 oxygen was involved in a hydrogen bond with Lys162 and Lys122 in AURKA and AURKB, respectively, whereas, the sulfonamide NH could catch ...
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Tags: Bioorg Med Chem Source Type: research