Abstract
Eleven novel naphthalimide-diamine conjugates were synthesized and their structures were confirmed by elemental analysis, 1H-NMR, 13C-NMR and MS. Their in vitro antitumor activities were assessed using MTT assays on two cancerous cell lines K562, HCT116, and one normal hepatoma cell line QSG 7701. Compound 7f exhibited potent antitumor activity on HCT116 cells and favorable cell selectivity toward QSG 7701 compared with the positive control, amonafide. Moreover, 7f could block HeG2 cells in the G2/M phase and induce HeG2 cells apoptosis. The interaction of compound 7f with herring sperm DNA was studied by UV/vis absorption and fluorescence spectroscopy under physiological conditions (pH = 7.4). The observed spectral quenching of compound 7f by DNA and the displacement of EB from DNA-EB complex by compound 7f indicated that compound 7f could intercalate into DNA base pairs, which was also corroborated by the effect of KI on compound-DNA interaction. Further caloric fluorescent tests revealed that the quenching mechanism was a static type. Meanwhile, the binding constants, thermodynamic parameters and the effect of NaCl on compound-DNA interaction showed that the type of interaction force was mainly hydrogen bonds and the binding process was driven by hydrogen and van der Waals bonding.
Highlights
As a common chemical motif, naphthalimides are among a growing class of compounds with desirable anticancer activity
The synthetic route to the naphthalimide-diamine conjugates 7a–k is shown in Scheme 1
The results showed that compound 7f could block HepG2 cells in the G2/M phase
Summary
As a common chemical motif, naphthalimides are among a growing class of compounds with desirable anticancer activity. Our previous work proved that conjugates 1–3 (Figure 1), composed of 1,8-naphthalimide units covalently attached to a polyamine such as spermidine or homospermidine, possessed remarkable cell selectivity through to human hepatoma Bel-7402 and human normal hepatocyte QSG-7701 trials [28,29]. Naphthalimide-polyamine conjugates have been proved to induce cancer cell apoptosis via different pathways [28,29,30]. These results encouraged us to screen more substituted naphthalimide-polyamine conjugates in order to assess their antitumor activity. There are rare reports on the interaction mechanism of naphthalimide-polyamine conjugates and DNA.
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