Abstract
A series of bis-naphthalimide derivatives with different diamine linkers were designed and synthesized. All of the synthesized bis-naphthalimide derivatives were characterized by NMR and HRMS spectra. The binding ability between the compounds and CT DNA was evaluated by using UV–Vis titration experiments. The bis-naphthalimide compound with an ethylenediamine linker showed the largest binding constant with CT DNA. Hence, it was used as the model compound to study the DNA binding selectivity by UV–Vis titration aiming at different DNA duplexes. As a result, this compound showed binding preference to AT-rich duplexes. The DNA binding modes of the compounds were also measured by viscosity titration. The cytotoxicity of the compounds was evaluated by MTT assay. Compounds with 1,6-diaminohexane or 1,4-phenylenedimethanamine linkers showed higher cytotoxicity compared with other bis-naphthalimide derivatives.
Highlights
Naphthalimide (1H-benzo[de]isoquinoline-1,3-(2H)-diones), a kind of flat heteroaromatic polycyclic amide, has been studied for decades due to its potential for the development of antitumor drugs [1]
The DNA binding constants and binding modes of the compounds were measured by UV–Vis titration and viscosity experiments
The results showed that the length of diamine linkers significantly influenced the binding ability of the bis-naphthalimide derivatives
Summary
Naphthalimide (1H-benzo[de]isoquinoline-1,3-(2H)-diones), a kind of flat heteroaromatic polycyclic amide, has been studied for decades due to its potential for the development of antitumor drugs [1]. To improve the antitumor activity and reduce the side effects, modifications on the naphthalimide structure have been carried out in recent decades; some naphthalimide derivatives with different side chains, aromatic ring systems, and substituents on the ring have been designed and synthesized [8,9,10,11]. The bis-naphthalimide Elinafide, which exhibits high activity against a series of human xenograft models, is a well-known bis-intercalator in all the naphthalimide derivatives [12]. Among all types of spacers, besides Tröger’s base moieties [14,15], polyamine spacers have been widely developed in the construction of bis-intercalators which exhibited high DNA binding ability and excellent anticancer activity [16,17,18,19,20]. Some other studies in the literature reported the influence of bis-naphthalimide derivatives with polyamine
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