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Comparative examination of the effects of DNA-affinic groups
attached to the bis-3-chloropiperidine molecule demonstrated
that the anthraquinone conjugate 1 is a distinctively more
potent DNA-interacting agents than the corresponding
naphthalene derivatives B1a and B1b, apparently on account of
its intercalative nature. Remarkably, our findings indicate that
compound 1 is capable to induce structural changes in DNA,
leading to the electrophoretic retardation of the double-stranded
DNA helix. These observations support our hypothesis that 1
binds to DNA via an intercalative mode. However, this mode of
action needs to be confirmed by a direct DNA intercalation
assay in future investigations. Consequently, it appears to be
worthwhile to explore further the potential of bis-3-
chloropiperidine 1 as a DNA-targeted conjugate with alkylating
and intercalating functionalities. In vitro cytotoxicity studies of
1 on different human cancer cell lines are currently underway.
17. a) Osheroff, N. DNA topology and enzymes; Humana Press:
Totowa, NJ, 1999; (in particular, chapter
2 and 3). b)
Gianoncelli, A.; Basili, S.; Scalabrin, M.; Sosic, A.; Moro, S.;
Zagotto, G.; Palumbo, M.; Gresh, N.; Gatto, B. ChemMedChem.
2010, 5, 1080.
Supplementary Material
Supplementary data (experimental procedures for the
synthesis of compounds 1–8, DNA cleavage assay and
sequencing gel analysis) associated with this article can be
found, in the online version, at:
Acknowledgements
This work was supported financially by MAECI, Ministero
Affari Esteri e Cooperazione Internazionale (Grant: PGR00171)
to B.G. The authors gratefully acknowledge the experimental
assistance of Alexander Francke and Irina Jülch. I.Z. thanks the
German National Academic Foundation (Studienstiftung des
deutschen Volkes) for providing a PhD scholarship, as well as
the International Giessen Graduate Centre for the Life Sciences
(GGL) and the German Academic Exchange Service (DAAD)
for a travel grant.
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