Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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Synthesis, Biological and Computational Evaluation of Novel Oxindole Derivatives as Inhibitors of Src Family Kinases

Author(s): Zühal Kilic-Kurt, Arzu Onay-Besikci, Sureyya Olgen.

Abstract:

In this present work, 5-chloro-3-(substituted-benzylidene)indolin-2-one and 1-benzyl-5-chloro-3-(substitutedbenzylidene) indolin-2-one derivatives were synthesized and evaluated for their inhibitory activity against Src Family Kinases (SFKs) such as Fyn, Lyn and Hck. 5-Chloro-3-(substituted)indolin-2-ones (3a - 6a) and 1-benzyl-5-chloro-3- (substituted-benzylidene)indolin-2-ones (3b - 6b) were prepared by condensation of 5-chloro oxindole and 1-benzyl-5- chloro oxindole with the equivalent amount of aldehydes in EtOH in the presence of piperidine. Among all compounds, only 4a, 5b and 6b were found slightly active against Fyn with 13 - 16% inhibitions at 0.1 and 0.01 mM concentrations. Compounds did not exhibit any inhibitory potency against Lyn and Hck. Docking study of compounds was performed to evaluate receptor-binding properties of compounds and the results showed that the most active compound 6b binds into the active site of Fyn, which has similar binding mode with potent inhibitor PP2.

Keywords: Oxindole derivatives, Inhibition of SFKs, Synthesis, Selectivity, Docking, Activity.

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Article Details

VOLUME: 10
ISSUE: 8
Year: 2013
Page: [713 - 718]
Pages: 6
DOI: 10.2174/15701808113109070023
Price: $58