Synthesis, cytotoxicity and apoptosis of naphthalimide polyamine conjugates as antitumor agents

Several naphthalimide polyamine conjugates were synthesized and evaluated for in vitro cytotoxicity against human leukemia K562, murine melanoma B16, Chinese hamster ovary CHO cell lines. Both triamine moieties and the length of spacers were crucial in elevating the potency of 1,8-naphthalimide. The typical compounds 5a and 5d exhibited excellent cell selectivity to cancer cells through the human hepatoma BEL-7402 and human normal hepatocyte QSG-7701 screens. In addition, 5d could disturb the cell cycle in B16 cells. The research on caspase activity and cytochrome c indicated that 5d could induce B16 cell apoptosis via both the mitochondrial and membrane death receptor pathways, and the Bcl-2 family numbers were involved in the control of apoptosis.

The introduction of triamine moieties could elevate greatly the potency of naphthalimide against several cell lines than their diamine counterpart. Compounds 5a and 5d exhibited excellent cell selectivity in cancer and normal cells. Compound 5d could disturb the cell cycle in B16 cells, and might induce B16 cell apoptosis via both the mitochondrial and membrane death receptor pathways.Figure optionsDownload as PowerPoint slide