Affiliation:
1. Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland
2. Avantor Performance Materials Poland S.A., ul. Sowinskiego 11, 44-101 Gliwice, Poland
Abstract
Background:
The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)-
diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction
disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken
strands of DNA.
Objective:
To investigate the influence of type of substituents and substitution positions in 1,8-
naphthalimde skeleton on the inhibition of Topoisomerase II activity.
Methods:
The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of
appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain
length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution
of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω-
hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines.
Results:
Antiproliferative activity of selected compounds against HCT 116 human colon cancer
cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial
epithelium cells was examined. Several of investigated compounds exhibit a significant activity
(IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with
concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared
with activity of Amonafide.
Conclusion:
The replacement of the nitro groups in the chromophore slightly reduces its anticancer
activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted
in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity,
moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and
cancer cells proliferation was observed.
Publisher
Bentham Science Publishers Ltd.
Cited by
6 articles.
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