Design and Synthesis of New Anticancer Pyrimidines with Multiple-kinase Inhibitory Effect

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Title Design and Synthesis of New Anticancer Pyrimidines with Multiple-kinase Inhibitory Effect
Author El-Deeb, Ibrahim Mustafa; Lee, So Ha
Journal Name Bioorganic & Medicinal Chemistry
Year Published 2010
Place of publication United Kingdom
Publisher Elsevier
Abstract A new series of N-substituted-2-aminopyrimidines based on the '4-(pyridin-3-yl)pyrimidin-2-amine' scaffold of Imatinib has been designed and synthesized. A selected group from the target compounds was tested over a panel of 60 cancer cell lines at a single dose concentration of 10 μM, and the two most active compounds, 25b and 30, were further tested in a five-dose testing mode to determine their IC50 values over the 60 cell lines. Compound 30 has showed good potencies and high efficacies, and was accordingly tested at a single dose concentration of 10 μM over a panel of 54 kinases. At this concentration, the compound has showed multiple inhibitions over a number of oncogenic kinases, including ABL1, AKT1, LCK, C-SRC, PIM1, FLT3, FYN, and KDR. A molecular modeling study was made by docking of the most active compound 30 and its inactive analog 29 into the kinase domain of ABL1 to investigate their possible binding interactions.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.bmc.2010.04.037
Volume 18
Issue Number 11
Page from 3860
Page to 3874
ISSN 0968-0896
Date Accessioned 2011-03-18
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Biologically Active Molecules
URI http://hdl.handle.net/10072/37819
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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