Al-Sanea, Mohammad M. Elkamhawy, Ahmed Paik, Sora Lee, Kyeong El Kerdawy, Ahmed M. Abbas, Bukhari Syed Nasir Roh, Eun Joo Eldehna, Wagdy M. Elshemy, Heba A. H. Bakr, Rania B. Farahat, Ibrahim Ali Alzarea, Abdulaziz, I Alzarea, Sami, I Alharbi, Khalid S. Abdelgawad, Mohamed A. 2024-01-19T17:03:48Z 2024-01-19T17:03:48Z 2022-01-25 2020-07 0968-0896 https://pubs.kist.re.kr/handle/201004/118417 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 mu M, 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 sub-panels. 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 hydrogen bond interaction with the surrounding amino acid residues Lys141, Glu260, and Asn261 in AURKA and Lys101, Glu177, and Asp234 in AURKB. Furthermore, N1 nitrogen of the quinoline scaffold formed an essential hydrogen bond with the hinge region key amino acids Ala213 and Ala173 in AURKA and AURKB, respectively. English PERGAMON-ELSEVIER SCIENCE LTD Sulfonamide-based 4-anilinoquinoline derivatives as novel dual Aurora kinase (AURKA/B) inhibitors: Synthesis, biological evaluation and in silico insights Article 10.1016/j.bmc.2020.115525 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.28, no.13 BIOORGANIC & MEDICINAL CHEMISTRY 28 13 N scie scopus 000540476700011 2-s2.0-85084207832 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article ANTIPROLIFERATIVE ACTIVITY ANTIINFLAMMATORY ACTIVITY SELECTIVE INHIBITORS POTENT AURORA B KINASE DESIGN VITRO BIOEVALUATION DISCOVERY APOPTOSIS Aurora Kinase A and B Molecular docking Synthesis 4-Anilinoquinoline Anticancer