Nucleus-targeting imaging and enhanced cytotoxicity based on naphthalimide derivatives

Organelles possess critical biological effects in cellular processes. However, the relationship between organelle targeting and antitumour activity is a challenging issue. In this paper, a number of amide/acylhydrazine modified naphthalimide derivatives were designed and synthesized. Interestingly, amide modified naph-thalimide derivatives NI-A-NH and NI-C-NH with (R)-piperdine and (S)-pyrrolidine functionalization exhibited enhanced cytotoxicity compared with acylhydrazine modified derivatives NI-A-2NH and NI-C-2NH. However, acylhydrazine modified derivatives NI-B-2NH and NI-D-2NH with (S)-piperdine and achiral piperdine conju-gates possessed better cytotoxicity than NI-B-NH and NI-D-NH with amide modifications. Fluorescence imaging, DNA binding interactions and cell cycle analyses were further completed to clarify that the nucleus-targeting effects showed enhanced cytotoxic activity, strong DNA binding and the blocking of cells in S phase. These re-sults provide a preliminary theoretical basis for the further design of organelle-targeting antitumour drugs.

Automated summary

This study designed and synthesized a series of modified naphthalimide derivatives, and found that different modifications had varying effects on cytotoxicity. The nucleus-targeting effects were shown to have a significant impact on cytotoxicity, DNA binding interactions, and cell cycle progression.