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of an antiestrogen. Initial tests show promising cell kill effects
superior to the responses elicited by either cisplatin or tamoxifen.
This observation warrants further studies on structure–activity
relationships in derivatives of the prototypical agent and their
in vivo efficacy against hormone-dependent breast cancer. Multi-
functional agents like compound 10 may have applications in
patients not responding to tamoxifen due to altered expression
levels of ER or an intrinsic inability to metabolize tamoxifen.26
This work was supported by the US National Institutes of
Health (grant CA101880) and a scholarship to X.Q. from the
China Scholarship Council (grant #2011694010).
Fig. 2 Differential response of MCF-7 cancer cells to compounds 5 and 10.
Notes and references
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hybrid in MCF-7 cells. While equipotent, both compounds can
be expected to induce cancer cell kill by different mechanisms.
A comparison of the drug-response profiles for compounds 5
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Here, we have presented the first conjugate that combines a
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drug responses for each derivative suggests that conjugate 10
acts by a distinct mechanism potentially involving interactions
with ER. Further investigation into the molecular mechanism of
the conjugate is necessary to substantiate this notion. Likewise, it
will be important to determine why introduction of an extended
linker in compound 100 results in a greatly diminished cytotoxic
response and if the activity of the components can be improved by
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In conclusion, the novel conjugate 10 was generated in an
attempt to combine the cytotoxic, DNA-damaging properties of a
nonclassical platinum–acridine agent with the targeting potential
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 2415--2417 2417