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through interactions with adjacent amino acids in the ATP binding
site.
These data suggest that further structural modifications in tet-
rahydroindazolone scaffold is required to convert them to more
potent Src kinase inhibitors such as phenylpyrazolopyrimidine
derivatives PP1 and PP2. Poor correlation between inhibition of
Src kinase and the cell proliferation could be due to the differential
cellular uptake and alternative mechanisms in antiproliferative
activities of the compounds.
In conclusion, an ecofriendly and regioselective method was
developed for the synthesis of 2-substituted THIs by one-pot
three-component coupling reaction of benzaldehydes, arylhydra-
zines, and 1,3-diones using Yb(OTf)3 as a catalyst in ionic liquid.
To the best of our knowledge, this is the first report of one-pot
synthesis and evaluation of THIs as Src kinase inhibitors and
anticancer agents. The synthesized compounds were evaluated
for c-Src kinase inhibitory activity and compound 32 showed
moderate inhibition of Src kinase with an IC50 value of 35.1
Compounds 15 and 16 consistently inhibited the cell proliferation
of SK-OV-3 and HT-29 cells by 49–62% at a concentration of 50 M.
lM.
l
Further structure–activity relationship studies are required for
optimizing the Src kinase inhibition and antiproliferative activities
of THIs.
Acknowledgments
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We thank University Grant Commission, New Delhi Project #
39-733/2010 (SR) and the American Cancer Society Grant #RSG-
07-290-01-CDD for the financial support.
Supplementary data
Supplementary data associated with this article can be found, in
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