Indolin-2-one derivatives as selective Aurora B kinase inhibitors targeting breast cancer.
Autor: | Dokla EME; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt. Electronic address: emanelawady@pharma.asu.edu.eg., Abdel-Aziz AK; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy., Milik SN; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt; School of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom., Mahmoud AH; Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland., Saadeldin MK; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy; Department of Biosciences, University of Milan, Milan 20133, Italy., McPhillie MJ; School of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom., Minucci S; Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy; Department of Biosciences, University of Milan, Milan 20133, Italy. Electronic address: Saverio.Minucci@ieo.it., Abouzid KAM; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt. |
---|---|
Jazyk: | angličtina |
Zdroj: | Bioorganic chemistry [Bioorg Chem] 2021 Dec; Vol. 117, pp. 105451. Date of Electronic Publication: 2021 Oct 24. |
DOI: | 10.1016/j.bioorg.2021.105451 |
Abstrakt: | Aurora B is a pivotal cell cycle regulator where errors in its function results in polyploidy, genetic instability, and tumorigenesis. It is overexpressed in many cancers, consequently, targeting Aurora B with small molecule inhibitors constitutes a promising approach for anticancer therapy. Guided by structure-based design and molecular hybridization approach we developed a series of fifteen indolin-2-one derivatives based on a previously reported indolin-2-one-based multikinase inhibitor (1). Seven derivatives, 5g, 6a, 6c-e, 7, and 8a showed preferential antiproliferative activity in NCI-60 cell line screening and out of these, carbamate 6e and cyclopropylurea 8a derivatives showed optimum activity against Aurora B (IC (Copyright © 2021 Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
Externí odkaz: |