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 study the influence of type of substituent and substitution position in 1,8-
naphthalimde skeleton on inhibition of Topoisomerase II activity.
Method: The starting 1,8-naphthalimide was prepared from acenaphthene by introduction of appropriate
substituents followed by condensation with ω-hydroxylakylamines of different chain
length. The substituent were introduced to 1,8-naphthalimide molecule by nucleophilic substitution
of leaving groups like nitro or bromo present in 4 or 4,5- position using the ω-
hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines.
Results: Antiproliferative activities 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 tumour 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 activities. 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.