Concise Article
MedChemComm
Conclusion
Benzothiophene acrylonitrile analogs 5, 6 and 13 have potent
anticancer properties that are likely mediated, at least in part,
through interference with tubulin polymerization. Unlike tax-
anes and Vinca alkaloids, these compounds are not substrates
for P-glycoprotein. Following treatment with compound 6, cells
appear to be dying by an atypical apoptosis mode, which is
consistent with mitotic catastrophe. This is signicant, since
many cancers have upregulated modes of apoptotic resistance
that render them difficult to treat.
Fig. 5 Tubulin immunofluorescence. Panel C demonstrates that compound 6
causes chromosome overduplication and formation of multiple spindle-poles. PC3
cells were treated with 100 nM docetaxel or 100 nM of compound 6 for 24 hours.
Green staining denotes tubulin and blue staining (DAPI) denotes the cell nuclei.
Acknowledgements
We are grateful to NCI/NIH (Grant number CA 140409) and to
the Arkansas Research Alliance (ARA) for nancial support and
to the NCI Developmental Therapeutic Program (DTP) for
screening data.
Notes and references
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This journal is ª The Royal Society of Chemistry 2013
Med. Chem. Commun.