Study on the Synthesis, Biological Activity and Spectroscopy of Naphthalimide-Diamine Conjugates

Abstract

Eleven novel naphthalimide-diamine conjugates were synthesized and their structures were confirmed by elemental analysis, 1 H-NMR, 13 C-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.

1,8‐Naphthalimide: A Potent DNA Intercalator and Target for Cancer Therapy

“…Number of other naphthalimide‐polyamines ( 8a–k ) has also been explored for their antitumor activities as well as intercalation potential by Tian et al . Compounds 8a–k have been reported to exhibit anticancer activities against HCT116 and K562 cells (Figure ).…”

Synthesis and the Biological Activity of Phosphonylated 1,2,3-Triazolenaphthalimide Conjugates

“…Naphthalimide derivatives such as mitonafide [21,22,23], amonafide [21,22,23,24,25], azonafide [26,27,28], DMP-840 [29] and elinafide (Lu-79553) [30,31] exhibit intercalating properties [21,22]. However, the clinical use of these compounds has been limited due to their low therapeutic indices as well as poor water-solubility [32]. In order to improve therapeutic properties of naphthalimides, many efforts have been undertaken towards synthesizing novel derivatives with higher activity and lower toxicity.…”

Spectroscopic Study on the Interaction between Naphthalimide-Polyamine Conjugates and Bovine Serum Albumin (BSA)

“…Similarly, polyamines can also bind to SA [11,12,13,14]. Naphthalimide-polyamine conjugates have been proven to exhibit good activity in vitro [15,16,17,18], intercalate DNA base pairs, and cause conformational variations in DNA [19]. MINS, a mononaphthalimide-polyamine conjugate, can bind to BSA, but causes a weak conformational change in BSA [20].…”