Organic Letters
Letter
NO in HCT116 cells in a dose-dependent manner, whereas 8
failed to release NO in HCT116 cells. Importantly, in
comparison with JS-K, 6 showed better selective inhibition of
HCT116 cancer cells while sparing noncancer cell CCD 841
CoN cells. Further alkaline comet assay indicated that 6 exhibited
more potent DNA ICL activity than JS-K. Collectively, these
results support the proposed mechanism of action as shown in
Figure 1B; i.e., in the absence of GSH/GST, the diazeniumdio-
late moiety in 6 masked its DNA ICLs activity, but in the
presence of GSH/GST in cancer cells the N,N-bis(2-TsO-
ethyl)amino moiety could be generated upon diazeniumdiolate
moiety release to exert potent DNA ICL activity together with
cytotoxicity of NO synergistically to enhance the anticancer
activity. The assessment of in vivo anticancer activity for 6 will be
conducted in the due course.
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37
38
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ASSOCIATED CONTENT
Supporting Information
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*
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(22) Maciag, A. E.; Nandurdikar, R. S.; Hong, S. Y.; Chakrapani, H.;
for all new compounds (PDF)
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AUTHOR INFORMATION
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*
*
2
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Notes
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557.
The authors declare no competing financial interest.
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A. W.; Fiebig, H. H.; Unger, C.; Kratz, F. J. Med. Chem. 1998, 41, 2701−
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ACKNOWLEDGMENTS
This work was supported by grants from the National Natural
Science Foundation of China (Nos. 81273378, 21372261, and
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1673305) and Jiangsu Province Funds for Distinguished Young
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Scientists (BK20160033). Part of the work was supported by the
opening project (SKL201513SIC) of the State Key Laboratory of
High Performance Ceramics and Superfine Microstructure,
Program for New Century Excellent Talents in University
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